Next Generation ORS: Randomized Controlled Trial Comparing ORS With Calcium vs Standard ORS in Reducing Severity With Acute Watery Diarrhea in Adults
Phase: PHASE2
Conditions: Diarrhea, Cholera
Sponsor: University of Florida

Study Protocol and Statistical Analysis Plan 
 
Research Protocol Title: Next generation ORS: Randomized controlled 
trial comparing ORS with calcium vs standard ORS in reducing severity 
with acute watery diarrhea of adults 
 
NCT05814042 
Version Dated 16.10.2022 
 

Project Summary 
[The summary, within a word limit of 300, should be stand alone and be fully understandable.] 
Principal Investigator: Dr. Shafiqul Alam Sarker 
Research Protocol Title: Next generation ORS: Randomized controlled trial comparing ORS with calcium vs 
standard ORS in reducing severity with acute watery diarrhea of adults 
Proposed start date: 1st September, 2022    
   Estimated end date: 31st December, 2023 
Background (brief): 
a. Burden: Globally, there are nearly 1.7 billion cases of childhood diarrheal illness every year, and 1.9
million children younger than 5 years die from diarrhea each year mostly in lower and middle income
countries. The deaths amount 18% of all deaths and is the second leading cause of death (after
pneumonia) in this age group.  Diarrheal disease is leading cause of malnutrition, growth failure and long
term cognitive deficit. The current recommendation of diarrhea management is to ensure proper hydration
through oral rehydration solution (ORS), continuedfeeding and zinc therapy. Although rehydration
therapy can replace losses of intestinal fluid and ions (Na+, K+, Cl- and HCO3- ), it reduces neither the
severity nor duration of diarrhea, and in some cases even worsens the diarrheal symptoms. Thus, over the
past several decades there have been continuous efforts to search for ways to not only rehydrate patients,
but to significantly decrease or even stop diarrheal losses.
b. Knowledge gap:Diarrhea causes monovalent (e.g., Na+, K+, Cl- and HCO3-) and divalent (e.g., Zn2+, Ca2+)
ion losses.   Unlike the losses of monovalent ions which are large and are therefore replaced through
rehydration therapy, the losses of divalent ions are relatively small in osmoles and are often overlooked
during diarrheal treatment. Relative to loss of Zn2+ (which is 3.4 times normal loss), the loss of Ca2+ to
diarrheal stool is far more severe, at about 20.5 times normal loss.  Studies now suggest that despite
divalent ions contributing relatively few osmoles in the stool, their effects are large due to the presence of
divalent ion-sensing receptors (e.g., Zn2+-sensing receptor, ZnSR; Ca2+-sensing receptor, CaSR) and their
amplifying effects in the gut. As a result, losses of these divalent ions without replacement may affect the
magnitude of, or recovery from acute diarrheal illnesses. Without replacement of Zn2+ and restoration of
ZnSR anti-diarrheal function, diarrhea is more severe and protracted; adding back Zn2+ and correcting
ZnSR defect reduce the severity and duration of diarrhea.
c. Relevance: This application seeks to improve diarrhea rehydration therapy by testing a novel
antidiarrheal concept: reduce diarrhea by activation of intestinal CaSR through replacement of lost Ca2+
during diarrhea. This idea is creative because it has not previously been described and tested. This
proposed study represents the first of such efforts.
Hypothesis (if any): We hypothesize that prompt replacement of lost Ca2+ and Zn2+ will significantly
reduce the severity and shorten the duration of diarrheal symptom
Objectives: We have two objectives
1. To examine if ORS with Ca2+ is more efficacious than standard ORS in reducing stool output and
diarrhea duration in severely dehydrated adults with cholera treated initially with IV fluid
2. To examine if ORS with Ca2+ is more efficacious than standard ORS in reducing stool output and
diarrhea duration in some-dehydrated adults with acute watery diarrhea.
Methods: We will conduct randomized, doubled-blinded, placebo-controlled clinical trial (RCT) at the 
Dhaka Hospital of International Centre for Diarrheal Disease Research, Bangladesh (icddr,b ). Over a 
period of 24 months, we plan to recruit 60 severely dehydrated adult patients infected with V. cholerae 
(Rapid diagnostic test (RDT+), (n=30/group x 2 groups) (Aim 1) and 336 some dehydrated adults with 
non-bloody acute diarrhea (n=168/group x 2 groups) (Aim 2). The Participants recruited will be 
randomised to receive new ORS with calcium (intervention) or standard WHO ORS (control) in hospital 
for 72 hours or up to the time when the patients fulfil the criteria of cessation of diarrhea, whichever is 
shorter.  

Outcome measures/variables: Quantitative diarrhoea parameters (stool output, duration of diarrhoea, stool 
frequency, percentage of patients who vomit, percentage of patients who require unscheduled intravenous 
therapy, and intake of ORS.     

Description of the Research Project 
 
Hypothesis to be tested: 
In a hypothesis testing research proposal, briefly mention the hypothesis to be tested and provide the scientific basis of the hypothesis, critically 
examining the observations leading to the formulation of the hypothesis. 
 
Does this research proposal involve testing of hypothesis: 
 No       
 Yes (describe below)  
 
We hypothesize that prompt replacement of lost Ca2+ will significantly reduce the severity and shorten 
the duration of diarrheal symptoms. 
 
Specific Objectives: 
Describe the specific objectives of the proposed study. State the specific parameters, gender aspects, biological functions, rates, and processes that will 
be assessed by specific methods. 
 
1. To examine if ORS with Ca2+ is more efficacious than standard ORS in reducing stool output and 
diarrhea duration in severely dehydrated adults with cholera. 
 
2. To examine whether ORS with Ca2+ is more efficacious than standard ORS in reducing stool 
output and diarrhea duration in some dehydrated adults with non-cholera non-bloody acute diarrhea. 
 
Background of the Project including Preliminary Observations: 
Provide scientific validity of the hypothesis based on background information of the proposed study and discuss previous works on the research topic, 
including information on sex, gender and diversity (ethnicity, SES) by citing specific references. Critically analyze available knowledge and discuss 
the questions and gaps in the knowledge that need to be filled to achieve the proposed aims. If there is no sufficient information on the subject, 
indicate the need to develop new knowledge.  
 
 
Treatment of infectious diarrhea remains a global challenge1,2. This is particularly so in infants and young 
children whose diarrhea is often severe and protracted. Without proper treatment, diarrhea can cause significant 
mortality and morbidity. According to UNICEF/WHO3, in 2008, diarrhea was the second leading cause of death 
in children under the age of 5 globally. Nearly one in every five child deaths - around 1.5 million a year - was due 
to diarrhea, which killed more children than AIDS, malaria, and measles combined. The mortality and morbidity 
of diarrhea remains today. In 2015, there were 2.39 billion estimated cases of diarrhea. Of these cases, 
approximately 957.5 million occurred in children under age 54. According to a recent article in NEJM5, diarrheal 
diseases remain the third leading cause of death in children under age 5 in Africa. In the United States from 2001-
2006, the cost of hospitalizations, emergency room visits and outpatient visits for diarrhea in pediatric patients 
was approximately $10 billion per year, not including indirect costs for the family. Notably, 77% of children 
visited an outpatient clinic for diarrhea by the age of five6. Importantly, most of the morbidity and mortality of 
diarrhea is not due to infection but dehydration and electrolyte imbalance. How to rehydrate diarrheal patients has 
become critical. 
 
 
Children with infectious diarrhea who become dehydrated are generally treated with oral rehydration solution 
(ORS) (e.g., Pedialyte) or intravenous rehydration therapy. Although currently recommended rehydration therapy 
can replace losses of intestinal fluid and ions (Na+, K+, Cl- and HCO3-), it reduces neither the severity nor duration 
of diarrhea7, and in some cases even worsens the diarrheal symptoms. Consequently, ORS is currently used in 
only one third of cases3,8. Thus, over the past several decades there have been continuous efforts to search for 
ways to not only rehydrate patients, but to significantly reduce or even stop diarrheal losses9-11.  
 
Importantly, diarrhea causes not only monovalent but also divalent ion (e.g., Ca2+ and Zn2+) losses, leading to a 
negative metabolic balance for these cations12,13.  However, while losses of monovalent ions are routinely 
replaced through ORS, losses of divalent ions (e.g., Ca2+) are often overlooked in diarrheal treatment. A deeper 
analysis of earlier metabolic balance data has revealed that the most dramatic ionic loss in diarrhea is actually not 
Na+ (which is 5.7x normal), K+ (which is 1.2x normal), Cl- (3.5x), HCO3- (2.2x) or Zn2+ (3.4x).  Instead, the 
largest loss is Ca2+, at about 20.5 times normal losses14 (Table 1).  
 

    
 
 
Given the presence of divalent cation-sensing receptors (e.g., Ca2+-sensing receptor, CaSR15,16) and their 
antidiarrheal effects in the intestine shown in recent studies17-26, a question arises of whether divalent cations lost 
in diarrhea should also be promptly replaced in diarrhea treatment. Without replacement of Zn2+ and restoration 
of Zn2+-sensing receptor (ZnSR) anti-diarrheal function,  
diarrhea is more severe and/or more protracted3; adding back Zn2+ and correcting the intestinal ZnSR defect27 
reduce diarrhea3. This is well documented. As a result, Zn2+ replacement during acute diarrhea has been adopted 
as policy in all countries3. However, despite the recent advances in Ca2+/CaSR research, limited information is 
available on the role and function of Ca2+/CaSR in diarrhea.  
 
 
 
DR. Cheng’s  laboratory at the University of Florida was the first to report the presence of a potent CaSR-based 
antidiarrheal mechanism in the gastrointestinal tract15,17,19. After having demonstrated its ‘inclusive’ antidiarrheal 
action (i.e., anti-secretory, pro-absorptive, anti-inflammatory and anti-motility) in laboratory animals17-26 (Fig. 1), 
we recently performed mechanistic studies to understand the changes of CaSR in diarrhea and the response to 
Ca2+ replacement using cultured human intestinal Caco-2 epithelium (Fig. 2).  
 

F ig
2 :
C F T R
(g re e n )
a n d
C a S R
(re d )
im m u n o flu o re s c e n c e
in
C a c o -2 c e lls . W h ile 9 0 m in tr e a tm e n t w ith c h o le ra to x in
(1 0 0 n M )
in d u c e s C F T R
tra ffic k in g to c e ll m e m b ra n e , it m o v e s C a S R
a w a y
fr o m
c e ll
m e m b ra n e
c a u s in g
in te rn a liz a tio n .
In c re a s in g
m e d iu m
C a 2 + fro m 1 .2 to 5 m M re v e rs e s th e s e p ro c e s s e s .
 
We found that without proper concentrations of Ca2+ in the extracellular environment, the enterocyte CaSR 
becomes internalized in response to pathogen exposure and loses its antidiarrheal function; by contrast, with 
proper Ca2+ concentrations, the CaSR returns to the plasma membrane and regains its function (Fig. 2). Similarly, 
upon exposure to pathogens animals develop more severe and protracted diarrhea when ORS contains no Ca2+ 
than when ORS contains Ca2+ (see Fig. 3). 
 
 
Fig 3: Diarrhea response to Ca2+ replacement in C57BL/6 mice. Cholera toxin (10 µg/mouse)
was gavaged into stomach to induce diarrhea. 90 min later, mice were allowed to drink ORS
(Pedialyte)±Ca2+, as indicated. N= 7-10. * P<0.05 vs. ORS.
** **
*
* * *
*
*
 
 
 
 This suggests that replacing lost Ca2+ in diarrhea could be beneficial. To further test this, we observed six 
diarrheic infants and children and compared their daily stool output before and after Ca2+ replacement14,22 (Fig. 
4). We found that shortly after Ca2+ replacement, diarrheal symptoms stopped14,22 (Fig. 4).  
 
 

F i g
4 : D ia r r h e a
r e s p o n s e
t o
C a 2 +
r e p l a c e m e n t in
a
1 0
y e a r
o l d
b o y
s / p
r e n a l
t r a n s p l a n t a t io n
w it h
p e r s is t e n t
n o r o v ir u s
a n d
c r y p t o s p o r id iu m
in f e c t io n .
A d d in g
b a c k
o f
C a 2 +
“ h a l t s ”
d ia r r h e a
p r o m p t l y a n d d r a m a t ic a l l y .
 
 
The next step is to conduct clinical trials to prove the concept. Based on our case studies, we expect the effect of 
Ca2+ replacement to be dramatic. Therefore, we would suggest a relatively small RCT to start, as this would be 
less expensive to conduct. The purpose of this small RCT study is to obtain pilot data to further quantify the size 
of effect of Ca2+ replacement on clinical outcomes (stool output and diarrhea duration) before a more powerful 
and more expensive RCT is performed. We hypothesize that prompt replacement of lost Ca2+ will significantly 
reduce the severity and shorten the duration of diarrheal symptoms. University of Florida has its tradition for 
translational research and is home to Gatorade – a drink for athletes that provides complete replacement of all 
electrolytes lost in sweat. The ultimate goal of this research is to generate a new Gatorade-like inexpensive ORS 
for people with diarrhea.   
Innovation 
This application seeks to improve diarrhea rehydration therapy by testing a novel antidiarrheal concept: activation 
of intestinal CaSR through replacement of lost Ca2+ during diarrhea. This idea is creative because it has not 
previously been described and tested. However, it has formidable therapeutic potential because, in contrast to 
current therapies that target single absorptive (e.g. “oral rehydration therapy”) or secretory component (e.g. Cl- 
channel inhibitors Crofelemer), the Ca2+/CaSR-based antidiarrheal therapy attacks multiple diarrhea-causing 
pathways. The latter include, but not limited to: 
 
● Reversal of intestinal secretion evoked by cholera toxin, E. coli enterotoxin STa and other   
secretagogues (NSP4). 
● Inhibition of secretagogue-induced intestinal bicarbonate loss. 
● Inhibition of intestinal electrolyte secretion evoked by exaggerated enteric nerve activity. 
● Enhancement of absorption of salt and solute (e.g., short-chain fatty acids). 
●Enhancement of tight junction and barrier function, and reduction of intestinal permeability, and 
suppression of gut inflammation. 
● Enhancement of intestinal microbial balance.  
● Correction of hypocalcemia and prevention of tetany. 
 
Thus, the therapy to be developed could potentially open up a new prevention/treatment mechanism for diarrhea 
overall not just childhood diarrhea. Moreover, because it exerts profound effects on diarrheal symptoms and is 
not just simply supportive as is the current ORS, it is expected to increase patient compliance rates and decrease 
not only the mortality and but also morbidity of diarrheal diseases. Finally, this innovation is appealing because it 
uses the naturally occurring, child-friendly mineral Ca2+ to treat diarrhea. Thus, if the results from the present 
study are promising, this simple affordable therapy will have clinical utility for billions of infants, children and 
adults worldwide. 
 
Rationale: 

According to the current WHO classification, dehydration is classified as “no”, “some” and “severe”. In patient 
studies, we propose to study both patients with severe dehydration (Aim 1), the group of diarrhea that has caused 
most of the diarrhea-associated deaths, and patients with some dehydration (Aim 2). We propose to study 
diarrhea with some dehydration rather than no dehydration because the former, normally requires medical 
treatment whereas the latter does not. We do not include diarrheal patients with no dehydration in this initial 
proposal also because of R21 tight budget. The reason why we propose to study both severe and some 
dehydration is for a maximal fund use consideration. Lastly, antibiotics used in Aim 1 will greatly limit the effect 
size. Including some dehydration patients that do not receive antibiotics (Aim 2) will provide a strong 
contingency if Aim 1 fails. The primary purpose of this proposal is to prove the concept and to determine the size 
of effect in order to guide the design of future RCTs. In these pilot studies, we do not plan to do etiology testing. 
In some respects, the etiology is not relevant. The primary interest is the diarrhea severity regardless of etiology. 
While it is of some interest to know whether any specific pathogen is an important variable effecting outcome, 
the present study is not powered for this. Nonetheless, we will do a stratified analysis by the type of infection as a 
secondary analysis, and correlate patients’ responses with stool pathogens detected at entry and assess if a better 
response is associated with any type of diarrhea in terms of etiology (bacterial vs. viral vs. parasitic).  The two 
ORS solutions are identical except that intervention ORS contains 10 mM Ca2+ whereas control ORS does not. 
Both solutions appear and taste similarly. The concentration of 10 mM Ca2+ is proposed because at this 
concentration extracellular Ca2+ had shown anti-secretory/anti-diarrheal effect, both in vitro, in perfused intestinal 
crypts15,17,19 and in vivo, in live animals (Fig. 3). This intervention ORS will provide 1500-2000 mg elemental 
Ca2+/day, which is equivalent to 1.5-2x RDA (recommended daily allowance) or 1.5-2 mEq/kg/day for a 50-kg 
adult assuming that he/she is rehydrated at a rate of 75ml/kg (some dehydration) or 100ml/kg (severe 
dehydration) per WHO guideline. This dose of Ca2+ also has anti-diarrheal action in patients with bacterial, viral 
and/or parasitic infections14,22 (Fig. 4). We propose to replace Ca2+ for 72 hours for the consideration of the 
relative short duration of acute infectious diarrhea28,29.   
 
Anticipated results/pitfalls/alternatives: 
Based on our preliminary studies, we anticipate that ORS with Ca2+ will reduce the volume of stool by 
approximately 30% compared to the control and shorten the mean duration of diarrhea by at least 1 day, in some 
or severely dehydrated patients. This is considered clinically meaningful as replacement of Zn2+, recommended 
by the WHO, is associated with a 25% reduction in the duration of acute diarrhea3. Resistant starch, which is also 
recommended by the WHO9, reduces the duration of diarrhea by 3-6 hours31. Another promising treatment 
adjunct that has recently received considerable attention is the use of probiotics. However, recent studies show 
that the use of probiotics shortens diarrhea in children only by 15 hours32 or has no effect at all33. On the other 
hand, Ca2+ is an ancient anti-diarrheal agent, and has been exploited by marine species to survive hyperosmotic 
(~1000 mOsm), high Ca2+ (~10 mM) seawater. Ca2+, through the CaSR, helps fish preserve water, avoid 
dehydration, and prevent occurrence of hypercalcemia34,35. Such antidiarrheal effects are preserved in 
mammals. In rodents, increased dietary Ca2+ intake was found 
to reduce diarrhea induced by various etiologies, including infectious (e.g., Salmonella enterocolitis36-39), 
chemically induced (e.g., DSS colitis40), and immune-mediated (e.g., colitis in HLA-B27 transgenic rats41); by 
contrast, lowering dietary Ca2+ intake in mice was found to increase diarrhea42. The anti-diarrheal effects of 
Ca2+ are also well-known in humans. For example, people subsisting on high-Ca2+ diets (such as dairy and 
cheese) or taking high Ca2+ supplements are often constipated, as are patients with hypercalcemia. Ca2+-
enriched tempeh and tofu (~3% of soybean dry weight) have long been utilized by the inhabitants of Indonesia 
and many other Oriental cultures to protect against diarrhea43-46. Along with Bovee-Oudenhoven, et al, we have 
recently demonstrated that supplementation of Ca2+ reduced diarrhea caused by enterotoxigenic Escherichia 
coli, Norovirus, and Cryptosporidium, with the mean duration reduced by at least 24 hours with no adverse effect 
other than mild reversible constipation22,47,48. Similar efficacy and safety were observed more recently by 
Sayyahfar et al 49, who showed that oral calcium gluconate replacement at a dose as low as 0.3 mEq/kg/day can 
shorten diarrhea duration by ~20%, although similar efficacy was not observed by Agustina, et al50. Agustina, et 
al examined effects of milk calcium phosphate intake on diarrhea occurrence and duration in healthy children 
aged 1-6 years and found no effect. The reason for this discrepancy is unclear; it may be related to the accuracy 
of data collected and the definition of diarrhea used. For example, the ‘positive’ study by Sayyahfar was 
performed in a hospital setting where diarrhea was defined using the WHO definition as ≥3 loose stools per day, 
whereas the ‘negative’ study by Agustina was performed in a 

community setting, in which diarrhea was based largely upon mothers’ report and was loosely defined using a 
broader definition of diarrhea as ≥2 loose stools per day. With this latter definition, some nonspecific 
noninfectious milder physiologic and osmotic forms of diarrhea that are commonly seen in the studied age group 
cannot be completely excluded. Indeed, in another study in which a more accurate stool measurement and a more 
definite infectious diarrhea were applied, the same calcium agent was found to reduce both stool output and 
diarrhea duration47. Our proposed clinical trials will be performed in the best equipped icddr,b, using the best 
validated WHO definition of diarrhea, and the most accurate method to quantitate stool output. We anticipate we 
are able to detect the anticipated impact of replacement of Ca2+ loss on stool output and diarrhea duration. 
Finally, we will do a stratified analysis by the type of infection as a secondary analysis. We will correlate 
patients’ responses with stool pathogen results obtained at entry and assess if a better response is associated with 
any type of diarrhea in terms of etiology (bacterial vs. viral vs. parasitic). However, based on current available 
data, this proposed therapy should work equally well in all types of infections as reported in our preliminary 
studies22,47,48,49 (Fig. 4), because it targets, not pathogens, but common downstream pathways leading to 
diarrhea (see the above Innovation section). 
As stated above, the dose of Ca2+ used is equivalent to 1.5-2x RDA, and we anticipate that the dose of Ca2+ is 
well tolerable and poses no health risk to diarrheal patients as demonstrated previously22,47,48 and in a recent 
study49. In fact, without concurrent administration of vitamin D, the bulk (~85%) of ingested Ca2+ remains 
unabsorbed in the lumen of the gut47,51. There, it produces local anti-diarrheal effects without causing unwanted 
systemic outcomes47,51. In infants, taking Ca2+ intake as high as 1750 mg/day (~6.7x RDA) was not found any 
health risk52. 
 
Research Design and Methods 
Describe the research design and methods and procedures to be used in achieving the specific aims of the research project. If applicable, mention the 
type of personal protective equipment (PPE), use of aerosol confinement, and the need for the use BSL2 or BSL3 laboratory for different part of the 
intended research in the methods.. Define the study population with inclusion and exclusion criteria, the sampling design, list the important outcome 
and exposure variables, describe the data collection methods/tools, and include any follow-up plans if applicable. Justify the scientific validity of the 
methodological approach (biomedical, social, gender, or environmental).  
 
Also, discuss the limitations and difficulties of the proposed procedures and sufficiently justify the use of them.  
 
We will conduct a randomized, doubled-blinded, placebo-controlled clinical trial (RCT) at the International 
Centre for Diarrheal Disease Research, Bangladesh (icddr,b). icddr,b is referred to as by many locals “cholera 
hospital” because it treats the world largest population of patients with diarrhea, particularly cholera. For the last 
2 years, 103,243-137,519 patients annually were treated in the Dhaka Hospital. These numbers were higher 
before COVID-19 pandemic. 12.2% were cholera and 44% were adults age 18-60 years.  
 
This will be a phase II-III randomized, double-blinded, placebo-controlled trial (RCT). Over a period of 18-24 
months, we will recruit 60 severely dehydrated adult patients treated for cholera (n=30/group x 2 groups) (Aim 1) 
and 336 some dehydrated adults with non-bloody acute diarrhea (n=168/group x 2 groups) (Aim 2) to receive 
new ORS (intervention) or standard WHO ORS (control) in hospital for 72 hours or up to the time when the 
patients fulfill the criteria of cessation of diarrhea, whichever is shorter. Clinical outcomes (stool output and 
diarrhea duration) will be assessed and compared. 
 
Specific Aim 1:  
To examine if ORS with Ca2+ is more efficacious than standard ORS in reducing stool output and diarrhea 
duration in severely dehydrated adults with cholera.   
 
Inclusion criteria: 
 
i. 
Adult male and female of any race or ethnicity  
ii. 
Age between 18 and 60 years 
iii. 
History of acute watery diarrhea (defined as the passage of ≥3 loose or watery stools in the past 24 hours) 
for less than 24 h before admission, with signs of severe dehydration (WHO criteria)  
iv. 
Stool positive for Vibrio cholerae, by rapid diagnostic test (Sayeed MA et al 2018) and successful 
rehydration with intravenous fluids within the first 6 h after admission (cholera group)  

v. 
Written informed consent. Participants or legal guardians (when patients are unable to provide consent 
themselves due to altered consciousness) will be requested for written informed consent for participation 
in the study. 
 
 
Exclusion criteria: 
i. 
Pregnancy as determined by history of last menstrual period,  
ii. 
Bloody diarrhea, 
iii. 
History of taking antibiotic or ant diarrheal mediation  
iv. 
Signs of systemic infection that needed intravenous antibiotics, or inability to rehydrate with intravenous 
fluid therapy in the first 6 h after admission. 
v. 
Not willing to participate in the study 
 
Prior treatments before randomization:  
 
Initially a health worker will screen the participants from the patients attending to Short Stay Unit (SSU) of 
icddr,b,. A demographic information and medical history will be obtained by a nurse. A clinical examination will 
be performed. Vital signs will be recorded. Dehydration status will be assessed using Dhaka method. If the 
participant is severely dehydrated, an intravenous fluids containing polyelectrolytes (Na+ 133 mM, K+ 13 mM, 
Cl- 98 mM, and acetate equivalent to 48 mM bicarbonate) will be initiated immediately at a rate of 100 ml/kg 
over 4-6 h, in addition to replacement of ongoing stool losses. ORS is also allowed as soon as the patient is able 
to drink.  A stool samples will be collected and tested for cholera by a rapid diagnostic test (RDT) Cholkit. 
(Sayeed MA et al 2018). If the rapid test for cholera is positive, the participant will be enrolled in study after 
taking informed consent (Specific aim 1). All patients will receive 1 gram of azithromycin and are initially 
rehydrated with intravenous  
 
Randomization: For this particular aim, 60 total participants will be enrolled and will be randomized to 2 arms: 
Arm 1: 30 ORS and arm 2:30 ORS+Ca2+. A permuted block randomization with variable block size will be used. 
Both types of ORSs will be packaged in an aluminum foil in the same manner) 
 
Procedure: 
 
Maintenance of oral therapy will begin immediately after completion of rehydration and continued until cessation 
of diarrhea or 72 h after randomization, whichever comes first.  During maintenance therapy, patients will 
consume the assigned ORS according to need, with a minimum volume equal to replacement of continued losses 
of watery or loose stool and emesis. All patients will be offered food (bread, banana) immediately after 
rehydration and standard meals (rice, fish or meat, vegetables, and lentils as practice in the Dhaka Hospital of 
icddr,b) three times daily thereafter. Plain water will be offered as desired, usually during the meals. If signs of 
dehydration appear during the maintenance phase, the calculated deficit will be replaced with standard ORS or 
the investigational ORS over 6 h with an interim assessment at 3 h.  Intravenous fluids will be administered only 
if signs of dehydration persist at the end of 6 h. If severe dehydration appears despite appropriate oral therapy, 
intravenous fluid therapy will be immediately started. Fluids will be infused according to the methods of the 
initial rehydration phase. Patients with serum Na+ concentration below 125 mmol/L and with clinical signs of 
hyponatremia (lethargy, poor response or no response to vocal commands), and patients with serum Na+ 
concentration below 120 mmol/L regardless of clinical signs of hyponatremia will be treated with 12 mL/kg 
bodyweight hypertonic (3% NaCl) saline solution. Patients will be removed from the study if they withdraw their 
informed consent, are transferred to Longer Stay Unit of the hospital for treatment of a severe underlying illness, 
continue with diarrhea for more than 72 h, or consume more than 30 L of the assigned ORS. Data collected on 
patients withdrawn from the study will be included in the analysis up to the time of withdrawal. 
 
Specific Aim 2:  
To examine if ORS with Ca2+ is more efficacious than standard ORS in reducing stool output and diarrhea 
duration in some-dehydrated adults with acute watery diarrhea.  
 
Inclusion criteria: 

i. 
Adult male and female of any race or ethnicity  
ii. 
Age between 18 and 60 years 
iii. 
History of acute watery diarrhea (defined as the passage of ≥3 loose or watery stools in the past 24 hours) 
for less than 24 h before admission, with signs of SOME dehydration (WHO criteria)  
iv. 
Stool negative for Vibrio cholerae, by rapid diagnostic test (Sayeed MA et al 2018)  
v. 
Written informed consent. Participants or legal guardians (when patients are unable to provide consent 
themselves due to altered consciousness) will be requested for written informed consent for participation 
in the study 
 
Exclusion criteria: Same as in Aim 1.  
i. 
Pregnancy as determined by history of last menstrual period,  
ii. 
Bloody diarrhea, 
iii. 
History of taking antibiotic or ant diarrheal mediation  
iv. 
Signs of systemic infection that needed intravenous antibiotics, or inability to rehydrate with intravenous 
fluid therapy in the first 4- 6 h after admission. 
v. 
Not willing to participate in the study 
 
  Prior treatments before randomization: 
 
As outlined above (Aim 1) CHRW will screen the participants for the study. Dehydration status will be assessed 
using Dhaka method. If the participant has some sign of dehydration, he/she will be provisionally selected and a 
stool sample will have tested for cholera by RDT.  The participant will be rehydrated initially with standard 
WHO ORS at a rate of 75 ml/kg over 4-6 hours in addition to replacement of ongoing stool losses. If the stool is 
negative, for cholera by RDT, the participant will be will be randomized. 
 
Randomization: 
Arm 1: 168 ORS and arm 2 168 ORS+ Ca2+.  A permuted block randomization with variable block size will be 
used. Assigned ORS is allowed to drink and will be continued until cessation of diarrhea or 72 h after 
randomization, whichever comes first 
 
Procedures:  
After initial rehydration and randomization, all cholera patients will receive antimicrobial therapy for cholera 
while all non-cholera patients will not. During maintenance therapy, patients will consume the assigned ORS 
according to standard of care WHO/icddr,b guidelines, with a minimum volume equal to replacement of 
continued losses of watery or loose stool and emesis. All patients will be offered food (bread, banana) 
immediately after rehydration and standard meals (rice, fish or meat, vegetables, and lentils as practice in the 
Dhaka Hospital of icddr,b) three times daily thereafter. Plain water will be offered as desired, usually during the 
meals. If signs of dehydration appear during the maintenance phase, the calculated deficit will be replaced with 
standard ORS or the investigational ORS over 6 h with an interim assessment at 3 h. Intravenous fluids will be 
administered only if signs of dehydration persist at the end of 6 h. If severe dehydration appears despite 
appropriate standard or interventional ORS, intravenous fluid therapy will be immediately started. Fluids will be 
infused according to the methods of the initial rehydration phase. Patients with serum sodium concentration 
below 125 mmol/L and with clinical signs of hyponatremia (lethargy, poor response or no response to vocal 
commands), and patients with serum sodium concentration below 120 mmol/L regardless of clinical signs of 
hyponatremia will be treated with 12 mL/kg bodyweight hypertonic (3% NaCl) saline solution. Patients will be 
removed from the study if they withdraw their informed consent, are transferred to Longer Stay Unit of the 
hospital for treatment of a severe underlying illness, continue with diarrhea for more than 72 h, or consume more 
than 30 L of the assigned ORS. Data collected on patients withdrawn from the study will be included in the 
analysis up to the time of withdrawal. 
 
Patients will be put onto a cholera cot and stool will be collected in a bucket, and weight measured on an 
electronic scale (Sartorius, Germany) that has a precision of 1 gram. Urine will be separated in a urine collector 
and volume measured with a calibrated cylinder. The volume of vomit will be measured by collection in a pre-
weighted bowl. Intake of ORS and free water will be measured by calibrated cylinder. Bodyweight in light 
clothing is measured on admission, at randomization, and every day thereafter until discharge, with an electronic 

scale (Sartorius) that has a precision of 1 gram. Scales are calibrated daily with standard weights. Patient will be 
discharged when diarrhea ceased. 
 
Cessation of diarrhea will be defined as the last watery or loose stool before passage of two consecutive soft or 
formed stools, or the beginning of 8 consecutive hours without any stool.  
 
Duration of diarrhea is the time in hours from randomization until cessation of diarrhea.  
 
Stool output is defined as the weight of stool in g per kg bodyweight after intravenous hydration and is to be 
expressed per 24 h or for the entire duration of diarrhea after randomization. 
 
At day 7, a cell phone call will be made to all participants to know the status of their disease. 
 
Clinical outcomes:  
 
Stool output will serve as the primary outcomes and will be assessed and compared.  
 
Secondary outcomes will include 1) Duration of diarrhea, defined as the time in hours from randomization until 
cessation of diarrhea, 2) stool frequency, 3) percentage of patients who vomit, 4) percentage of patients who 
require unscheduled intravenous therapy, and 5) intake of ORS. High calcium intake may occasionally cause 
local gastrointestinal irritation/vomiting30. 
 
Potential Risks: 
 
These include 1) physical discomfort during baseline and follow up phlebotomies or bruising or infection at the 
site of blood draw; 2) psychological stress from interruption of daily routine, blood withdrawals or providing 
personal health information to investigators. None of these is deemed significant risks to subject health. Blood 
withdrawal will be performed by skilled, research-oriented nursing staff under antiseptic conditions. Blood 
withdrawal sites will be carefully inspected for signs of infiltration or inflammation throughout each procedure. 
To minimize psychological stress, subjects will be seated comfortably in a reclining chair during blood 
withdrawal. They will be able to return to their regular activities or hospital care during the study days and have 
free access to food and water allowed by his/her medical condition. 
 
Researchers will take appropriate steps to protect any personal health information they collect. However, there is 
a slight risk that information about a subject could be revealed inappropriately or accidentally. Depending on the 
nature of the information, such a release could upset or embarrass that person, or possibly affect his/her 
insurability or employability. Calcium is a key active ingredient in the new ORS and is a basic nutrient. This new 
ORS is estimated to provide patients within the recommended ~1-2x RDA doses and is therefore not anticipated 
detrimental. This is particularly true in diarrheic patients in whom the metabolic balance for Ca2+ is known to be 
negative due to its significant losses from diarrhea. To ensure the safety of our study subjects, however, we will 
still monitor serum and urine Ca2+. If hypercalcemia or hypercalciuria occurs, such subjects will be called in and 
be monitored carefully until the problem resolves. 
 
We describe herein the general strategy to be employed in responding to adverse events (AEs), serious adverse 
events (SAEs) and suspected unexpected serious adverse reactions (SUSARs). Operative definitions for this trial 
that are acceptable to the FDA, Health Canada and EU countries are: 
 
• Adverse Event (AE): Any untoward medical occurrence in a clinical trial subject administered an 
investigational product that does not necessarily have causal relationships with the treatment. This may include 
an unfavorable or unintended sign, symptom or disease temporarily associated with the use of the investigational 
drug, whether or not considered related to the drug product. 
 
• Serious Adverse Event (SAE): Any AE that results in death, is life-threatening, requires hospitalization or 
prolongation of hospitalization or results in persistent or significant disability. 
 

• Suspected Unexpected Serious Adverse Reaction (SUSAR): Any SAE that is possibly related to the study 
treatment and is unexpected. These events are reported to the University of Florida  within 24 hours. Mild, 
asymptomatic increases or decreases in serum electrolytes and specific or nonspecific gastrointestinal symptoms 
are potential AEs, not SAEs or SUSARs, because they are expected and not even considered serious, unless the 
symptom was debilitating or required hospitalization. Moreover, these are also known complications of the 
underlying disease. In contrast, an SUSAR might be a serious arrhythmia or seizure, the onset of which occurred 
proximate to administration of the study product; both would be unanticipated to occur in response to ORS.  
Researchers will take appropriate steps to protect any personal health information they collect. Each staff member 
will be trained in how to protect PHI, which includes keeping records locked, discussions should be held in a 
private setting, using password protected devices, and not sharing data with non-study staff. However, there is a 
slight risk that information about a subject could be revealed inappropriately or accidentally. Depending on the 
nature of the information, such a release could upset or embarrass that person, or possibly affect his/her 
insurability or employability. 
 
Adequacy of Protection against Risks  
  
 The study will be conducted in compliance with the procedures outlined in the protocol, the International 
Conference on Harmonization's Good Clinical Practice (ICH_GP), and in accordance with the ethical guidelines 
and local regulatory requirements for the trial. The protocol will be submitted to local Independent Institutional 
Review Board (IRB) comprising Research Review Committee (RRC) and Ethical Review Committee (ERC) for 
approval, as well as the University of Florida IRB.  
  
a. Informed Consent  
 
Written, informed consent will be obtained from all eligible participants prior enrollment into the study after 
explanation of the aims, procedures, risks, benefits, and rights for participation and refusal to the study, and 
assurances regarding confidentiality of personal and medical information. If any questions arise, study 
physician or investigator will answer those questions. Signature (or thumbprint, if illiterate) of each of the 
participants will be obtained before their enrollment in the study and prior to any study-related activity. A 
witness and study personnel who obtains the consent must sign and date in the informed consent form. The 
participants will be provided with a copy of the signed consent form for their retention. All consent forms will 
be collected and compiled in hard copy and will be stored in a safe and locked cabinet.  
  
b. Protections Against Risk  
 
As stated above, we anticipate a low risk of study. However, if a subject is harmed as a direct result of his/her  
participation in this study, the sponsor will pay for all reasonable and necessary medical expenses required to 
treat the injury, as long as:  
1) The injury occurs during participation in the study;   
2) The injury results directly from the study product or study-related procedures that the person 
would not have received as part of his/her routine medical care as determined by the DSMB (see 
below).  
We will maintain the confidentiality that includes documentation, laboratory data, clinical and other related 
information. The privacy, anonymity and confidentiality of the information provided by participants will strictly 
be maintained. Information will be kept confidential and will not be used for any other purpose than the study. 
Maintenance of confidentiality of the data will be strictly practiced and restrictions on access to data forms will 
be enforced. Original source documents, data files, study records, and reports will be maintained by the Principal 
Investigator. Information derived from the participants will be used for research purposes only and would not be 
shared anywhere by the name of the participants 
 
Protection of human subjects, AE and DSMB:  
 

The dose of Ca2+ used is equivalent to 1.5-2x RDA, and we anticipate no health risk, although high Ca2+ intake 
may occasionally cause some local gastrointestinal adverse event (AE) such as vomiting30. Though the reported 
vomiting was mild and reversible30, we will document and monitor this event and compare it. We will request 
IRB in Gainesville and Dhaka to constitute a DSMB to oversee data relating to safety. The initial responsibility 
of the DSMB will be to approve the initiation of this clinical trial. After this approval, the DSMB will review the 
data of primary and secondary endpoints, data for early termination of trial (stopping rules), or AE. The board 
will meet twice per calendar year, after the interim analysis, and or whenever there is an issue or concern. The 
DSMB will recommend changes in the study, including discontinuation, if significant trends in safety are 
identified.  
 
Availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device 
Exemption (IDE) Status - Patient Study 
 
Provide a summary describing the availability of study agents and support for the acquisition and administration 
of the study agent(s): 
 
In this proposed clinical study, the investigational agent Next Generation ORS (oral rehydration solution) will be 
tested against the current standard control ORS in diarrheic patients with cholera (aim1) and non-cholera 
infections (aim2) in order to assess its safety and efficacy in treating diarrhea. Both study agents are available. 
These same investigational agents have been tested in animals in our Phase I STTR. 
 
We have contacted the FDA - no IND/IDE approval is required for this study. 
 
Potential Benefits of the Proposed Research to Research Participants and Others 
 
Patients who enroll into the study will receive at least three days’ hospital care of their disease free of charge. The 
benefits to others include advancing knowledge about Next Generation ORS and developing a novel therapy for 
diarrheal diseases. The risks associated with this research are limited to providing personal health information 
and minimal blood withdrawal and are therefore considered very small in relation to the anticipated benefits 
accrued by the participant and to the society. 
Blinding and Code Breaking Procedure   
 
Since the test and comparator ORS will identical in package and dose, this study will be randomized, double 
blind study. Study investigators along with the study staff involved in the clinical care, IP administration, safety 
evaluation and laboratory analyses will be blinded regarding the treatment assignment to the participants. The 
code will not be revealed until the end of the trial, data entry and data cleaning is completed. If the intervention 
assignment unblended, all collaborator or/and sponsor of the study will be notified.  
 
  Participant withdrawal from the study 
 
The participants are allowed to discontinue or withdraw from the study anytime during the study period. There 
will be no replacement for such withdrawals. The investigator(s) might also withdraw the participants from the 
study, if in his/her clinical opinion, that is in the best interest of participant concerned or if it is considered to be 
non-compliant to the protocol. A participant might also be withdrawn due to protocol violation, death, or early 
termination of the study by the Sponsor. 
 
Wherever possible, the tests and evaluations at termination visit will be carried out. The withdrawal will not be 
included in the analyses. 
 
Materials  
Health data and blood, stool and urine specimens, will be obtained. The local hospital clinical lab will proceed 
and analyze the blood, urine and stool specimens collected from patients by the trained research team. 
Interviews and examinations will be conducted by the trained research staff physicians/nurses at icddr,b at 
Dhaka.  

 
Protected health information may be collected, used, and shared with others to determine if a subject can 
participate in the study, and then as part of his/her participation in the study. This information can be gathered 
from the subject or his/her past, current or future health records, from procedures such as physical examinations, 
x-rays, blood or urine tests or from other procedures or tests. Dr. Li, whose role is lead statistician, will 
supervise data management.   
 
Sample Size Calculation and Outcome (Primary and Secondary) Variable(s) 
Clearly mention your assumptions. List the power and precision desired. Describe the optimal conditions to 
attain the sample size. Justify the sample size that is deemed sufficient to achieve the specific aims. 
 
In Aim 1, we plan to enroll 60 patients (30/group x 2 treatment groups). The sample size will yield 
an 80% statistical power to detect clinical outcome difference of the stool volume between intervention ORS and 
WHO ORS groups, with the use of the planned t-test at 0.05 level, assuming an effect size of 68 g/kg, which is 
~30% reduction from control group (mean total stool output in control group=212 g/kg) and considering a 15% 
attrition rate (i.e., complete data for 52 patients).  
 
In Aim 2, we plan to enroll 336 patients (168/group x 2 treatment groups). The sample size will yield an 80% 
statistical power to detect clinical outcome difference of the stool volume between intervention ORS and WHO 
ORS groups, with the use of the planned t-test at 0.05 level, assuming an effect size of 15 g/kg, which is 30% 
reduction from control group (mean total stool output in control group=50 g/kg) (S.A. Sarker, unpublished 
observation) and considering a 15% attrition rate (i.e., complete data for 286 patients).  
 
Data Analysis 
Describe plans for data analysis, including stratification by sex, gender and diversity. Indicate whether data 
will be analysed by the investigators themselves or by other professionals. Specify what statistical software 
packages will be used and if the study is blinded, when the code will be opened. For clinical trials, indicate if 
interim data analysis will be required to determine further course of the study. 
 
Intent-to-treat analysis will be considered throughout the analysis stage. Standard summary statistics including 
mean and standard deviations (SD) for continuous variables and frequency tables for categorical 
variables will be provided by treatment groups for outcome measures. Appropriate transformations such as 
natural-log will be used as necessary on variables to comply with normality. Figures such as scatter plots will be 
constructed to visualize the data. The primary study outcome measure stool output will be compared between the 
two groups with a two-sample t-test or a nonparametric Wilcoxon rank sum test at two-sided significance level of 
0.05. Regression models will be employed as well if potential confounders such as age, gender, type of infection, 
and severity of dehydration need to be adjusted in the analysis. Secondary study outcome measures will be 
analyzed in a similar fashion. For binary outcomes including “stool frequency”, “vomit” and “require 
unscheduled intravenous therapy”, 2 by 2 tables with chi-square tests will be conducted 
to compare the two groups. Logistic regression models will be used to compare the binary outcomes as well when 
potential confounders need to be adjusted. Missing data (if any) will be handled with multiple imputation 
assuming missing at random. If it is not missing at random, we will consider a sensitivity analysis to study the 
impact of missing data on the analysis results. 
 
Data Safety Monitoring Plan (DSMP) 
All clinical investigations (research protocols testing biomedical and/or behavioural intervention(s)) should 
include the Data and Safety Monitoring Plan (DSMP). The purpose of DSMP is to provide a framework for 
appropriate oversight and monitoring of the conduct of clinical trials to ensure the safety of participants and 
the validity and integrity of the data. It involves involvement of all investigators in periodic assessments of 
data quality and timeliness, participant recruitment, accrual and retention, participant risk versus benefit, 
performance of trial sites, and other factors that can affect study outcome. 
 
In Dhaka, the local Ethical Review Committee (ERC) will be requested to constitute a local DSMB to oversee at 
interval the progress of the trial and safety of the investigational product in Dhaka. The DSMB will comprise of 

3-5 members including biostatistician, medicine specialist, a pharmacologist, and a clinical researcher from 
icddr,b or other institute in Bangladesh. The initial responsibility of the DSMB will be to approve the initiation of 
this clinical trial. After this approval, the DSMB will review the data of primary and secondary endpoints (safety 
and efficacy), data for early termination of trial (stopping rules), or adverse events. The board will meet twice per 
calendar year, after the interim analysis, and whenever there is an issue or concern. The DSMB will recommend 
changes in the study, including discontinuation, if significant trends in safety or efficacy are identified earlier 
than expected. None of DSMB members will be involved in the study in any way. 
 
The board will meet twice per calendar year, after the interim analysis, and whenever there is an issue or concern. 
The DSMB will recommend changes in the study, including discontinuation, if significant trends in safety or 
efficacy are identified earlier than expected. 
 
To minimize risk of data leak, Dr. Li, whose role is lead statistician, will supervise data management. We will use 
secure on-line data entry that directly stores the data on protected and dedicated servers. This process facilitates 
data entry and collection, and offers optimal security for collecting research-related information. The proposed 
Data Management will be housed within the Data Coordinating Center at the UF Clinical and Translational 
Science Institute (CTSI). A remote data-entry platform will be constructed for study coordinators in both study 
sites (UF and icddrb) to view and/or enter data according to a defined set of read/write permissions. This data 
entry platform will include real-time error checking based on either range or relational checks. The database will 
monitor access down to the data-field level and track the user, time 
and date for each successful data submission. Additionally, the data management group will provide a public 
website, including an overview of study information, background and responsibilities of key personnel, news 
items, conference information and announcements, information for potential study subjects; and a secure website 
including access to the Manual of Procedures, reports to the steering committee and funding agency, minutes of 
conference calls with study investigators, reports and updates on recruitment status. 
 
 
 
Ethical Assurance for Protection of Human rights 
Describe the justifications for conducting this research in human participants. If the study needs observations 
on sick individuals, provide sufficient reasons for using them. Indicate how participants’ rights will be 
protected, and if there would be benefit or risk to each participants of the study. Discuss the ethical issues 
related to biomedical and social research for employing special procedures, such as invasive procedures in 
sick children, use of isotopes or any other hazardous materials, or social questionnaires relating to individual 
privacy. Discuss procedures safeguarding participants from injuries resulting from study procedures and/or 
interventions, whether physical, financial or social in nature. [Please see Guidelines] 
 
The study will be conducted in compliance with the procedures outlined in the protocol, the International 
Conference on Harmonization's Good Clinical Practice (ICH_GP) and in accordance with the ethical guidelines 
and local regulatory requirements for the trial. The protocol will be submitted to local Independent Institutional 
Review Board (IRB) comprising Research Review Committee (RRC) and Ethical Review Committee (ERC) for 
approval, as well as the University of Florida IRB. 
 
 We anticipate this is a low risk of study. However, if a subject is harmed as a direct result of his/her 
participation in this study, the sponsor will pay for all reasonable and necessary medical expenses required to 
treat the injury, as long as: 
1) The injury occurs during participation in the study; 
2) The injury results directly from the study product or study-related procedures that the person would not have 
received as part of his/her routine medical care as determined by the DSMB. 
 
Use of Animals 
Describe if and the type and species of animals to be used in the study. Justify with reasons the use 
of particular animal species in the research and the compliance of the animal ethical guidelines for 
conducting the proposed procedures. 

 
No animals will be used in the study. 
 
Collaborative Arrangements 
Describe if this study involves any scientific, administrative, fiscal, or programmatic arrangements 
with other national or international organizations or individuals. Indicate the nature and extent of 
collaboration and include a letter of agreement between the applicant or his/her organization and the 
collaborating organization. 
 
The study is being conducted under a Sponsored Research Agreement with national Institute of Health (NIH), 
USA in collaboration with (Dr. Cheng X Sam, Associate Professor and Pediatric Gastroenterologist, Department 
of Pediatrics at the University of Florida College of Medicine,    Clinical & Translational Science Institute 
(CTSI), University of Florida (UF), Dr. Eric Nelson, Assistant Professor, Department of Pediatrics, and Emerging 
Pathogens Institute (EMI), University of Florida and George J , Fuchs, Pediatric Gastroenterologist  and  
Professor; Vice Chair of Clinical Affairs for the Department of Pediatrics. Kentucky University, USA. Dr. Cheng 
will be the lead PI of the study. 
 
The University of Florida is among the top public research university in the nation, has its tradition 
for translational research and is home to Gatorade, whereas the icddr,b is the international diarrheal study center 
that has played a major role in the discovery and implementation of ORS for the treatment of diarrhea, including 
cholera. Both institutions have adequate support for clinical research services including CTSI. The PI Dr. Cheng 
is a physician-scientist and provides a novel anti-diarrheal concept, while the co-I Drs. Sarker, Fuchs and Nelson 
have actively been conducting clinical studies on diarrhea in icddr,b and can help bringing this discovery into a 
bedside therapy. This combination is wellsuited to complete the proposed studies. Dr. Li is a biostatistician @ UF 
CTSI. 
 
 
Facilities Available 
Describe the availability of physical facilities at site of conduction of the study. If applicable, 
describe the use of Biosafety Level 2 and/or 3 laboratory facilities. For clinical and laboratory-based 
studies, indicate the provision of hospital and other types of adequate patient care and laboratory 
support services. Identify the laboratory facilities and major equipment that will be required for the 
study. For field studies, describe the field area including its size, population, and means of 
communications plus field management plans specifying gender considerations for community and 
for research team members. 
 
Institutional Overview  
icddr,b 
 
icddr,b is a unique global resource integrating research, humanitarian care and teaching to improve the health of 
billions of people living in poverty across the globe and in its host country of Bangladesh. icddr,b’s current 
strategic plan reinforces its legacy of focusing not just on discovery, but also on strengthening the organization’s 
ability to shape policy at the national, regional and global level, as well as advocating for the use of highly 
effective products and evidence-based discoveries. Integral to its research, icddr,b provides treatment through its 
urban and rural hospitals and clinics in Bangladesh, which ensures that evidence-based solutions are 
implementable - world oriented while also providing high quality care, free of charge, to over 200,000 
Bangladeshis annually. Amazingly, icddr,b's case fatality rate for diarrhea, which represents the vast majority of 
its case load is virtually zero percent in the absence of co-morbidity.  
  
Research Strength and Capabilities  
 

icddr,b has a longstanding track record in the interdisciplinary research which underpins the Hub, and in 
maximizing its impact for the benefit of our population in Bangladesh as well as in other low and middle income 
countries. This is evidenced by the fact that we led the drafting of the National Nutrition Policy of Bangladesh 
and reviewed the Nutrition background paper that informed the country’s Seventh Five Year Plan.   
  
Comprising one of the largest, multi-disciplinary cohorts of scientists in the developing world, icddr,b 
collaborates with dozens of international academic, research, and development partners to develop and share 
global lifesaving solutions. icddr,b addresses some of the most critical health challenges facing the world today, 
including neonatal survival, maternal and child health, chronic diseases, enteric diseases, malnutrition, 
communicable and non-communicable diseases, emerging infectious diseases, neglected tropical diseases, 
poverty and equity and gender issues, and population and climate change with innovative, evidence-based and 
cost-effective public health solutions.   
  
The proposed study will be conducted in Dhaka Hospital of Nutrition & Clinical Services Division (NCSD) of 
icddr,b; that provides cost free care and treatment to more than 140 000 patients each year. The patient 
population comprised of 40% adults and 60% children. The Dhaka Hospital is equipped with Short Stay Unit for 
uncomplicated diarrhea patients, Longer Stay Unit for diarrheal patients with associated co-morbidities and 
Intensive Care Unit. Additionally, the Dhaka Hospital is equipped with a Study Ward to support clinical trial.  
  
The Laboratory Sciences and Services Division (LSDD) of icddr,b hosts some of the finest research laboratories 
and its clinical diagnostic laboratories serve as reference laboratories for clinical diagnostic analysis of human 
disease cohorts and control subjects. The diagnostic laboratories are the only accredited labs under ISO15189 
(quality) and ISO15190 (safety) in Bangladesh for as many as 160 different tests and parameters. A state of art 
animal house and a bacteriological media facility also cater to the requirements of the researchers from within 
icddr,b and outside collaborators. The LSSD has always carried out and supported field based and clinical 
research programs and trials through its laboratory based solutions and platforms besides its flagship diagnostic 
laboratories.  
  
Team’s Strength  
The Nutrition & Clinical Services Division (NCSD) of icddr,b; which carries out most of the clinical research, 
research in nutrition and food security has a highly skilled multidisciplinary research team experienced in 
conducting studies spanning the full spectrum of nutrition and food security, randomized control trial to 
community-based intervention trials and informing policy.  
 
Facilities and Resources – University of Florida  
  
The University of Florida (UF) is one of only 17 public, land-grant universities that belong to the prestigious 
group of 61 academic research institutions that comprise the Association of American Universities. With more 
than 50,000 students, including approximately 15,000 graduate and professional degree students, the University 
is the fifth largest in the nation. UF is a major teaching and research institution with more than 200 educational 
programs and external research grants and contracts of over $600 million in the past year. Nationally, UF ranks 
among the top 15 public universities in research funding.  
  
As a land grant university, UF, in collaboration with the U.S. Department of Agriculture and local county 
governments, administers the Florida Cooperative Extension Service (CES). With offices in all 67 counties of the 
state of Florida, the CES is dedicated to making knowledge available that will enhance and sustain quality of life. 
In addition to traditional services in agriculture and the natural sciences, the CES offers major programs in health 
and nutrition education throughout the state of Florida. Coordination with the CES offers an ideal environment 
for dissemination and implementation of health intervention programs. 
   
The UF Clinical Research Center (CRC) is the CTSA-funded Clinical and Translational Science Institute (CTSI) 
and is available to Dr. Cheng when needed. The CRC serves as the University’s principal venue for state of the 
art patient-oriented investigations into the causes, prevention and treatment of human disease. It includes a 10 
bed inpatient ward, a discrete outpatient area, and dedicated space for exercise physiology. Other resources 

include a Nutrition Research Unit/Metabolic Kitchen, a Data Services Laboratory with work stations and bio 
statistical support and a Core Laboratory.  
The study will be conducted in Study ward or Short stay unit of Dhaka Hospital of icddr, b. 
 Dhaka Hospital was established by icddr,b in 1962 primarily to meet the urgent need to treat patients, 
particularly children, with severe diarrheal disease. It has since grown into a nationally important centre treating 
more than 140,000 patients a year. It acts as a beacon illustrating what can be achieved by a hospital facility even 
within a developing world setting. Dhaka Hospital provides an infrastructure for a wide range of clinical research 
projects. It also plays a critical role in areas such as disease surveillance, monitoring for antimicrobial resistance 
and clinical training. 
Dhaka Hospital offers a full range of services, particularly for diarrheal and respiratory disease, with infants and 
children representing a high proportion of patients. It delivers outstanding care, saving an estimated 40,000 lives 
that might otherwise be lost every year. 
 
Literature Cited 
Identify all cited references to published literature in the text by number in parentheses. List all cited 
references sequentially as they appear in the text. For unpublished references, provide complete 
information in the text and do not include them in the list of Literature Cited. There is no page limit 
for this section, however, exercise judgment in assessing the “standard” length. 
 
1. Black, R. et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. 
The Lancet 375, 1969-1987 (2008).  
2.  Moore, S., Lima, A. A. M. & Guerrant, R. Infection: Preventing 5 million child deaths from diarrhea in 
the next 5 years. Nature Review Gastroenterology Hepatology 8, 363-364, 
doi:10.1038/nrgastro.2011.103. (2011). 
3. UNICEF/WHO. Diarrhoea: Why children are still dying and what can be done? Geneva. (2009). 
4. Collaborators, G. B. D. D. D. Estimates of global, regional, and national morbidity, mortality, and 
aetiologies of diarrhoeal diseases: a systematic analysis for the Global Burden of Disease Study 2015. 
The Lancet. Infectious diseases 17, 909-948, doi:10.1016/S1473-3099(17)30276-1 (2017). 
5. Reiner, R. C., Jr. et al. Variation in Childhood Diarrheal Morbidity and Mortality in Africa, 2000-2015. 
The New England journal of medicine 379, 1128-1138, doi:10.1056/NEJMoa1716766 (2018). 
6. Cortes, J. E., Curns, A. T., Tate, J. E. & Parashar, U. D. Trends in healthcare utilization for diarrhea and 
rotavirus disease in privately insured US children <5 years of age, 2001-2006. The Pediatric infectious 
disease journal 28, 874-878, doi:10.1097/INF.0b013e3181a653cd (2009). 
7. Harrell, J. E. & Cheng, S. X. Inability to reduce morbidity of diarrhea by ORS: can we design a better 
therapy? Pediatric research, doi:10.1038/pr.2017.295 (2018). 
8. Sreerama reddy, C. T., Low, Y. P. & Forsberg, B. C. Slow progress in diarrhea case management in low 
and middle income countries: evidence from cross-sectional national surveys, 1985-2012. BMC Pediatr 
17, 83, doi:10.1186/s12887-017-0836-6 (2017). 
9. Binder, H. J., Brown, I., Ramakrishna, B. S. & Young, G. P. Oral rehydration therapy in the second 
decade of the twenty-first century. Current gastroenterology reports 16, 376, doi:10.1007/s11894-014-
0376-2 (2014). 
10. Donowitz, M. et al. Translational approaches for pharmacotherapy development for acute diarrhea. 
Gastroenterology 142, e1-9, doi:10.1053/j. gastro.2012.01.014 (2012). 
11. Farthing, M. J. Antisecretory drugs for diarrheal disease. Digestive Diseases 24, 47-58 (2006). 
12. Lewis, L. D. & Phillips, R. W. Water and electrolyte losses in neonatal calves with acute diarrhea. A 
complete balance study. Cornell Vet 62, 596-607 (1972). 
13. Castillo-Duran, C., Vial, P. & Uauy, R. Trace mineral balance during acute diarrhea in infants. The 
Journal of pediatrics 113, 452-457 (1988). 

14. Fraebel, J. et al. Extracellular Calcium Dictates Onset, Severity, and Recovery of Diarrhea in a Child 
with Immune-Mediated Enteropathy. Frontiers in pediatrics 6, 7, doi:10.3389/fped.2018.00007 (2018). 
15. Cheng, S. X. Calcium-sensing receptor: A new target for therapy of diarrhea. World J Gastroenterol 22, 
2711-2724, doi:10.3748/wjg. v22.i9.2711 (2016). 
16. Tang, L. et al. The Extracellular Calcium-Sensing Receptor in the Intestine: Evidence for Regulation of 
Colonic Absorption, Secretion, Motility, and Immunity. Frontiers in physiology 7, 245, doi:doi: 
10.3389/fphys.2016.00245 (2016). 
17. Cheng, S. X. Calcium-sensing receptor inhibits secretagogue-induced electrolyte secretion by intestine 
via the enteric nervous system. American Journal of Physiology-Gastrointestinal and Liver Physiology 
303, G60-G70, doi:10.1152/ajpgi.00425.2011 (2012). 
18. Cheng, S. X., Geibel, J. & Hebert, S. Extracellular polyamines regulate fluid secretion in rat colonic   
crypts via the extracellular calcium-sensing receptor. Gastroenterology 126, 148-158 (2004). 
19.  Cheng, S. X., Okuda, M., Hall, A., Geibel, J. P. & Hebert, S. C. Expression of calcium-sensing receptor 
in rat colonic epithelium: evidence for modulation of fluid secretion. American Journal of Physiology-
Gastrointestinal and Liver Physiology 283, G240-250 (2002). 
20. Geibel, J. et al. Calcium-sensing receptor abrogates secretagogue-induced increases in intestinal net fluid 
secretion by enhancing cyclic nucleotide destruction. The Proceedings of the National Academy of 
Sciences of the United States of America 103, 9390-9397 (2006). 
21. Cheng, S. X. et al. Epithelial CaSR Deficiency Alters Intestinal Integrity and Promotes Proinflammatory 
Immune Responses. FEBS Lett 588, 4158-4166, doi: 10.1016/j.febslet.2014.05.007 (2014). 
22. Cheng, S. X., Bai, H. X., Gonzalez-Peralta, R., Mistry, P. K. & Gorelick, F. S. Calcium ameliorates 
diarrhea in immunocompromised children. Journal of pediatric gastroenterology and nutrition 56, 641-
644, doi:10.1097/MPG.0b013e3182868946 (2013). 
23. Tang, L. et al. Calcium-Sensing Receptor Stimulates Cl-- and SCFA-dependent but Inhibits cAMP-
dependent HCO3- Secretion in Colon. The American journal of physiology 308, G874-883, 
doi:10.1152/ajpgi.00341.2014 (2015). 
24. Sun, X., Tang, L., Winesett, S., Chang, W. & Cheng, S. X. Calcimimetic R568 inhibits tetrodotoxin-
sensitive colonic electrolyte secretion and reduces c-fos expression in myenteric neurons. Life sciences, 
doi: 10.1016/j.lfs.2017.12.019 (2017). 
25. Tang, L., Jiang, L., McIntyre, M. E., Petrova, E. & Cheng, S. X. Calcimimetic acts on enteric neuronal 
CaSR to reverse cholera toxin-induced intestinal electrolyte secretion. Scientific reports 8, 7851, 
doi:10.1038/s41598-018- 26171-4 (2018). 
26. Tang, L. et al. Bumetanide increases Cl--dependent short-circuit current in late distal colon: Evidence for 
the presence of active electrogenic Cl- absorption. PloS one 12, e0171045, doi: 
10.1371/journal.pone.0171045 (2017). 
27. Sunuwar, L., Asraf, H., Donowitz, M., Sekler, I. & Hershfinkel, M. The Zn2+-sensing receptor, 
ZnR/GPR39, upregulates colonocytic Cl- absorption, via basolateral KCC1, and reduces fluid loss. 
Biochimica et biophysica acta 1863, 947-960, doi: 10.1016/j.bbadis.2017.01.009 (2017). 
28. Fleisher, G. R. Approach to diarrhea in children in resource-rich countries., 
<https://www.uptodate.com/contents/approach-to-diarrhea-in-children-in-resource-richcountries? 
source=search_result&search=acute diarrhea pediatrics & selected Title=2~150. > ( 
29. Alam, N. H., Majumder, R. N. & Fuchs, G. J. Efficacy and safety of oral rehydration solution with 
reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study 
group. Lancet 354, 296- 299 (1999). 
30. Cheng, S. X., Bai, H. X., Gonzalez-Peralta, R., Mistry, P. K. & Gorelick, F. S. Calcium ameliorates 
infectious diarrhea in immune compromised children. J Pediatr Gastroenterol Nutr (in press). 
31. Raghupathy, P. et al. Amylase-resistant starch as adjunct to oral rehydration therapy in children with 
diarrhea. Journal of pediatric gastroenterology and nutrition 42, 362-368 (2006). 

32. Dinleyici, E. C. et al. Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric 
outpatient setting. Jornal de pediatria 91, 392-396, doi: 10.1016/j.jped.2014.10.009 (2015). 
33. Schnadower, D. et al. Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children. 
The New England journal of medicine 379, 2002-2014, doi:10.1056/NEJMoa1802598 (2018). 
34. Nearing, J. et al. Polyvalent cation receptor proteins (CaRs) are salinity sensors in fish. Proceedings of 
the National Academy of Sciences of the United States of America 99, 9231-9236 (2002). 
35. Whittamore, J. M., Cooper, C. A. & Wilson, R. W. HCO (3) (-) secretion and CaCO3 precipitation play 
major roles in intestinal water absorption in marine teleost fish in vivo. The American journal of 
physiology 298, R877-886, doi:10.1152/ajpregu.00545.2009 (2010). 
36. Bovee Oudenhoven, I. M., Termont, D. S., Heidt, P. J. & Van der Meer, R. Increasing the intestinal 
resistance of rats to the invasive pathogen Salmonella enteritidis: additive effects of dietary lactulose and 
calcium. Gut 40, 497- 504 (1997). 
37. Bovee Oudenhoven, I. M., Wissink, M. L., Wouters, J. T. & Van der Meer, R. Dietary calcium phosphate 
stimulates intestinal lactobacilli and decreases the severity of a salmonella infection in rats. The Journal 
of nutrition 129, 607- 612 (1999). 
38. Bovee-Oudenhoven, I. M., Termont, D. S., Weerkamp, A. H., Faassen-Peters, M. A. & Van der Meer, R. 
Dietary calcium inhibits the intestinal colonization and translocation of Salmonella in rats. 
Gastroenterology 113, 550-557 (1997). 
39. Bovee-Oudenhoven, I., Termont, D., Dekker, R. & Van der Meer, R. Calcium in milk and fermentation 
by yoghurt bacteria increase the resistance of rats to Salmonella infection. Gut 38, 59-65 (1996). 
40. Cheng, S. X. Calcium-sensing receptor in the gut: evidence for its role in mediating known nutritional 
therapy for inflammatory bowel disease. JPGN 55, E70 (2012). 
41. Schepens, M. A. et al. Supplemental calcium attenuates the colitis-related increase in diarrhea, intestinal 
permeability, and extracellular matrix breakdown in HLA-B27 transgenic rats. J Nutr. 139, 1525-1533, 
doi:10.3945/jn.109.105205 (2009). 
42. Pele, L. C. et al. Low dietary calcium levels modulate mucosal caspase expression and increase disease 
activity in mice with dextran sulfate sodium induced colitis. J Nutr. 137, 2475-2480 (2007). 
43. Tofu may offer protection against diarrhea. http://thesoyfoodscouncil.com/tofu-may-offer-protection-
againstdiarrhea/, <http://thesoyfoodscouncil.com/tofu-may-offer-protection-against-diarrhea/> ( 
44. Karyadi, D. & Lukito, W. Beneficial effects of tempeh in disease prevention and treatment. Nutrition 
reviews 54, S94-98 (1996). 
45. Karyadi, D. & Lukito, W. Functional food and contemporary nutrition-health paradigm: tempeh and its 
potential beneficial effects in disease prevention and treatment. Nutrition 16, 697 (2000). 
46. Soenarto, T., Sudigbia, I., Hermana, Karmini, M. & Karyadi, D. Antidiarrheal characteristics of tempe 
produced traditionally and industrially in children aged 6-24 months with acute diarrhea., 174-186 
(Indonesian Tempe Foundation, 1997). 
47. Bovee-Oudenhoven, I. M. J., Lettink-Wissink, M. L. G., Van Doesburg, W., Witteman, B. J. M. & Van 
Der Meer, R. Diarrhea caused by enterotoxigenic Escherichia coli infection of humans is inhibited by 
dietary calcium. Gastroenterology 125, 469-476 (2003). 
48. Tang, L. & Cheng, S. X. Does activation of CaSR represent a new method to reduce secretory and 
inflammatory diarrhea? Journal of pediatric gastroenterology and nutrition 60, 17 (2015). 
49. Sayyahfar S., Sadeghian. M. & Amrolalaei M. The effect of calcium on the duration of acute 
gastroenteritis in children: A randomized clinical trial. Med J Islam Repub Iran 35:83 (2021). 
50. Agustina R, et al. Randomized trial of probiotics and calcium on diarrhea and respiratory tract infections 
in Indonesian children. Pediatrics 129(5): e1155-64 (2012) 
51. Gueguen, L. & Pointillart, A. The bioavailability of dietary calcium. J Am Coll Nutr 19, 119S-136S 
(2000). 

52. Sargent, J. D., Dalton, M. A., O'Connor, G. T., Olmstead, E. M. & Klein, R. Z. Randomized trial of 
calcium glycerophosphate-supplemented infant formula to prevent lead absorption. The American journal 
of clinical nutrition 69, 1224-1230 (1999). 
 
 
 
Budget: Approved budget attached at the end. 
 
Budget Justifications 
Please provide one page statement justifying the budgeted amount for each major item, including the use of 
human resources, major equipment, and laboratory services. 
 
International Centre for Diarrhoeal Disease Research, Bangladesh 
Personnel 
icddr,b salaries as listed are inclusive of all benefits, and are approved by the icddr,b finance office. Given the 
potential for substantial inflation in Bangladesh, icddr,b expects annual increases in the salaries of approximately 
5-7% for International Staff and 10% for local staff. Annual FTE calculations for staff are based on the period in 
which study activities will be implemented. 
 
Dr. Shafiqul Alam Sarker is based full-time in Dhaka and will be local PI of the study and will give effort 10% 
of his time to lead the study team in implementing the study as per SOP following the approved protocol 
throughout the study period. He will be responsible for the design and conceptual framework of the study and 
provide strategic guidance to the team, support ethical approval process, response to external reviewers, data 
analysis, report writing and dissemination. He will also guide quality about the study activities. 
 
Dr. Shamima Sultana Co- Investigator/ functional PI is full time based in Dhaka. She is medical graduate with 
public health background. She will coordinate all the related activities of the project by supervising overall study 
activities according to SOP. She will be involved in hiring and training process of all the study personnel. Besides 
she will be responsible to supervise the clinical activities by the nurses and Project Research Physician. She will 
provide 10% of her time through the whole study period. 
 
Senior Budget Coordinator: Allocated 5% of time for budget planning and financial analyst for 16 months. He 
will support on budget preparation, review of budget, financial tracking and reporting as per project need. 
 
Project Research Physician (PRP): Two PRP will be Involved. One of them will provide 100% of time for 16 
months and another one will involve100% of time for 12 months. They will be responsible for screening and 
enrolling study participants, clinical case management and tracking discharge of the participant 
 
Administrative/Finance Officer: We will need 20% time of an Administrative/Finance Officer who will be 
involved directly in hiring process, signing agreement, logistic management etc. 
 
Study Nurse (3): Prescreening of patients from registration desk, assist PRP in consenting procedure, 
enrollment. Will be responsible for hospital care and management of participants. 
 
Health worker (3): Help study nurse in selection of eligible patients from triage, inward day to day Pt care and 
provide full time. 
 

Data Management Assistant: One DMA PRP will be involved and will provide 100% of time 12 months for 
data record and analysis. 
 
Study Expenses: Funds totaling ~$12,500 per year are request to pay for all non-salary costs to complete the 
study at the icddr,b. These funds will cover Hospitalization Cost, Lab Test, IRB, Consumable Supplies, etc. 
 
Other Support 
Describe sources, amount, duration, and grant number of all other research funding currently 
granted to PI or under consideration.  
 
No additional financial support has been sought for this project. 
 
 

Biography of the Investigators 
Provide biographical data in the following format for all key personnel including the Principal 
Investigator. Copy the same format for each of them. 
Note: Biography of the External Investigators may, however, be submitted in the format as 
convenient to them.. 
 
1. Name: Dr Shafiqul Alam Sarker 
 
2. Present Position: Senior Scientist 
 
3. Educational background: (last degree and diploma & training relevant to the present research 
proposal) 
 
 
Institution 
Year 
Degree 
MBBS   (Rajshahi University, Bangladesh) 
1977 
 
MD       (University of Basel, Switzerland) 
1991 
 
PhD      (Karolinska Institute, Sweden) 
2006 
 
FRCP    (Royal College of Physician, Edinburgh) 
2017 
Training 
Fellowship in Nutrition and Clinical Research 
1979-1981 
Training 
Upper GI endoscopy and Ultrasound 
1996 
 
4. Ethics Certification: 
 
 
 
If Yes 
 
 
Issuing Authority 
Registration No 
Valid Until 
No 
   
Yes  
 
NIH 
2560152 
2022 
 
Note: If the response is “no”, please get certification from CITI or NIH before study 
initiation and submit a copy to the Committee Coordination Secretariat 
 
5. List of ongoing research protocols/ activities   
        
Protocol/ 
Activity 
Number 
Role in the protocol/ 
activity (PI, Co-PI, Co-I)  
Starting date 
End date 
Percentage of 
time 
PR-15089 
PI 
08.06.2016 
31.12.2020 
65% 
ACT-01013 
PI 
07.11.2018 
31.12.2020 
30% 
PR-17083 
Co-I 
01.10.2017 
30.04.2019 
5% 
 
6. Publications  
 
 
Types of publications 
Numbers 
a. Original scientific papers in peer-review journals                                
110 
b.   Peer reviewed articles and book chapters                                                   
4 
c. Papers in conference proceedings 
- 
d. Letters, editorials, annotations, and abstracts in peer-reviewed journals   
35 
e. Working papers 
3 
f. Monographs 
- 
 
 

 
7. Five recent publications including publications relevant to the present research protocol 
1. Sarker SA, Sultana S, Reuteler G, Moine D,  Descombes P, Charton F, Bourdin G, McCallin 
S, Ngom-Bru C, Neville T, Akter M, Hoq S, Qadri F, Talukdar K,  Kassam M,  Delley M,  
Loiseau C,  Deng Y, El Aidy S, Berger B,  Brüssow H. Oral Phage Therapy of Acute 
Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From 
Bangladesh. EBioMedicine. 2016 Jan 5;4:124-37 
2. Sarker SA, Ahmed T, Brussow H. Persistent diarrhea: A persistent infection with 
enteropathogens or a gut commensal dysbiosis? Environmental Microbiology; 2017 
19(10):3789-3801. 
3. Kieser S, Sarker SA, Berger B, Sultana S, Chisti MJ, Islam SB, Foata F, Porta N, Betr B, 
Fournier C, Descombes P, Mercenier A, Sakwinska O, Brüssow H. Antibitic Treatment 
Leads to Fecal Escherichia coli and coliphage expansion in Severely Malnourished diarrheal 
Patients. Cell Mol Gastroenterol Hepatol. 2017 Dec 13;5(3):458-460.e6. 
4. Kieser S, Sarker SA, Sakwinska O, Foata F, Sultana S, Khan Z, Islam S. Porta N, 
Combremont S, Betrisey B, Fournier C, Charpagne A, Descombes P, Mercenier A, Berger 
B, Brüssow H. Bangladeshi Children with Acute Diarrhea Shows Fecal microbiome with 
Increased Streptococcal Abundanc irrespective of diarrhea etiology. Environ Microbiol. 
2018 May 22. doi: 10.1111/1462-2920.14274. 
5. Kienesberger S, Perez-Perez GI, Olivares AZ, Bardhan P, Sarker SA, Hasan KZ, Sack RB, 
Blaser MJ. When Helicobacter pylori is acquired in populations in developing countries; A 
birth-cohort study in Bangladesh? Gut Microbes. 2018 Mar 1:1-12.  

 
1. Name: Dr Tahmeed Ahmed 
 
2. Present Position: Senior Director, Nutrition and Clinical Services Division, icddr,b and 
Professor of Public Health Nutrition, James P. Grant School of Public Health, BRAC 
University 
 
3. Educational background: (last degree and diploma & training relevant to the present research 
proposal) 
 
 
Institution 
Year 
Degree 
PhD, University of Tsukuba, Japan 
1996 
Degree 
MBBS, University of Dhaka 
1983 
Training 
Clinical training in Pediatrics, University of Tsukuba 
Hospital 
1990-1992 
Training 
Residential training in Pediatrics, Dhaka Shishu 
Hospital 
1989-1990 
 
4. Ethics Certification: 
 
 
 
If Yes 
 
 
Issuing Authority 
Registration No Valid Until 
No 
   
Yes 
 
NIH 
1933611 
Issued on 12 August 
2015 
 

Note: If the response is “no”, please get certification from CITI or NIH before study 
initiation and submit a copy to the Committee Coordination Secretariat 
 
5. List of ongoing research protocols/ activities   
        
Protocol/ Activity Number 
Role in the protocol/ 
activity (PI, Co-PI, 
Co-I)  
Starting date 
 
End date 
Percentage 
of time 
Childhood acute illness and 
nutrition (CHAIN) study 
Co-I 
01.11.2016 
31.08.2019 
10% 
Antibiotics for childhood 
diarrhea (ABCD) trial 
Co-PI 
01.02.2017 
30.04.2020 
20% 
Bangladesh Environmental 
Enteric Dysfunction (BEED) 
Study 
PI 
01.11.2015 
30.04.2020 
15% 
Evaluation of the largest 
stunting control program - 
Suchana 
Co-PI 
01.06.2016 
31.12.2020 
20% 
Microbiota directed 
complementary food clinical 
trials (Primary MAM and Post 
SAM-MAM) 
PI 
01.11.2018 
27.02.2021 
20% 
 
6. Publications  
 
 
Types of publications 
Numbers 
a. Original scientific papers in peer-review journals                                
286 
b.   Peer reviewed articles and book chapters                                                   
18 
c. Papers in conference proceedings 
25 
d. Letters, editorials, annotations, and abstracts in peer-reviewed journals   
5 
e. Working papers 
14 
f. Monographs 
1 
 
7. Five recent publications including publications relevant to the present research protocol 
7.1. Nahar B, Hossain M, Ickes SB, Naila NN, Mahfuz M, Hossain D, Denno DM, Walson 
J, Ahmed T. Development and validation of a tool to assess appetite of children in low 
income settings. Appetite 2018 Dec 21. pii: S0195-6663(18)30468-9.  
7.2. Ahmed T, Choudhury N, Hossain I, Tangsuphoom N, Islam MM, de Pee S, Steiger G, 
Fuli R, Sarker SA, Parveen M, West KP, Christian P. Development and acceptability 
testing of ready-to-use supplementary food made from locally available food ingredients 
in Bangladesh. BMC Pediatr 2014 Jun 27; 14:164.  
7.3. Subramanian S, Huq S, Yatsunenko T, Haque R, Mahfuz M, Alam MA, Benezra A, 
DeStefano J, Meier MF, Muegge BD, Barratt MJ, VanArendonk LG, Zhang Q, Province 
MA, Petri WA Jr, Ahmed T, Gordon JI. Persistent gut microbiota immaturity in 
malnourished Bangladeshi children. Nature 2014 doi:10.1038/nature13421.  
7.4. Khatun H, Comins CA, Shah R, Islam MM, Choudhury N, Ahmed T. Uncovering the 
barriers to exclusive breastfeeding for mothers living in Dhaka’s slums: a mixed method 
study. Int Breastfeed J 2018 Sep 26; 13:44. 

7.5. Ahmed T, Auble D, Berkley JA, Black R, Ahern PP, Hossain M, Hsieh A, Ireen S, 
Arabi M, Gordon JI. An evolving perspective about the origins of childhood 
undernutrition and nutritional interventions that includes the gut microbiome. Ann N Y 
Acad Sci 2014 Aug 12.    
 
 
 
 
Certificate of Completion 
The National Institutes of Health (NIH) Office of Extramural Research 
certifies that Tahmeed Ahmed successfully completed the NIH Web-
based training course “Protecting Human Research Participants”. 
Date of completion: 12/08/2015  
Certification Number: 1933611  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

1. Name: Dr. Shamima Sultana 
 
2. Present Position: Senior Programme Manager, NCSD, icddr,b 
 
3. Educational background: (last degree and diploma & training relevant to the present 
research proposal) 
 
 
Institution 
Year 
Degree 
 MBBS (University of Dhaka, Bangladesh) 
1994 
Degree 
 MPH ((NIPSOM, University of Dhaka, Bangladesh) 
2006 
Training 
Fellowship (Swiss Federal Institute of Technology Zürich 
(ETH), Switzerland 
2007 
Training 
Australian Leadership and Management (Fellowship course in 
Griffith University, Brisbane, Queensland, Australia) 
2014 
 
4. Ethics Certification: 
 
 
 
If Yes 
 
 
Issuing 
Authority 
Registration No 
Valid Until 
No 
   
Yes  
 
NIH 
 2983111 
Issued 21 September, 2022 
 
Note: If the response is “no”, please get certification from CITI or NIH before study 
initiation and submit a copy to the Committee Coordination Secretariat 
 
Already received training certificate on International Conference on Harmonization (ICH) and 
Good Clinical Practice (GCP) from Macro Care Clinical Research Ltd and Max-Neeman Int, India.  
 
5. List of ongoing research protocols/ activities   
        
Protocol/ 
Activity Number 
Role in the protocol/ 
activity (PI, Co-PI, Co-I)
Starting date 
 
End date 
Percentage 
of time 
PR-15089 
Co-PI 
08.06.2016 
31.12.2020 
0% 
PR-
19045 
Co-I 
07.11.20
18 
31.08.202
2 
100 % 
 
6. Publications  
 
 
Types of publications 
Numbers 
g. Original scientific papers in peer-review journals                                
17 
h.   Peer reviewed articles and book chapters                                                  
1 
i. Letters, editorials, annotations, and abstracts in peer-reviewed journals   
- 
j. Working papers 
3 
 
7. Five recent publications including publications relevant to the present research protocol 
7.1. Rahman MM, Ghoshal UC, Sultana S, Kibria MG, Sultana N, Khan ZA, Ahmed F, Hasan 
M, Ahmed T, Sarker SA. Long-Term Gastrointestinal Consequences are Frequent Following 
Sporadic Acute Infectious Diarrhea in a Tropical Country: A Prospective Cohort Study The 
American Journal of Gastroenterology volume 113, pages1363–1375 (2018) 

7.2. Shawna McCallin, Shafiqul A. Sarker,  Shamima Sultana, Frank Oechslin and Harald Brüssow.  
Metagenome analysis of Russian and Georgian Pyophage cocktails and a placebo-controlled 
safety trial of single phage versus phage cocktail in healthy Staphylococcus aureus carriers 
Environmental Microbiology (2018) 20(9), 3278–3293 
7.3. Shamima Sultana, Shafiqul A. Sarker and Harald Brussow. What happened to Koch’s 
postulates in diarrhoea Environmental Microbiology (2017) 19(8), 2926–2934 
7.4. Kieser S, Sarker SA, Berger B, Sultana S, Chisti MJ, Islam SB, Foata F, Porta N, Betr B, 
Fournier C, Descombes P, Mercenier A, Sakwinska O, Brüssow H. Antibitic Treatment Leads 
to Fecal Escherichia coli and coliphage expansion in Severely Malnourished diarrheal Patients. 
Cell Mol Gastroenterol Hepatol. 2017 Dec 13;5(3):458-460.e6. 
7.5. Shafiqul Alam Sarker, Shamima Sultana, Gloria Reuteler, Deborah Moine, Patrick Descombes,c 
Florence Charton, Gilles Bourdin, Shawna McCallin and Harald Brüssow. Oral Phage Therapy 
of Acute Bacterial Diarrhea with Two Coliphage Preparations: A Randomized Trial in Children 
From Bangladesh. EBioMedicine. 2016 Feb; 4: 124–137. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

BIOGRAPHICAL SKETCH 
Provide the following information for the Senior/key personnel and other significant contributors. 
Follow this format for each person.  DO NOT EXCEED FIVE PAGES. 
NAME: Cheng, Sam Xianjun 
eRA COMMONS USER NAME (credential, e.g., agency login): SAMCHENGMD 
POSITION TITLE:  Associate Professor of Pediatric Gastroenterology 
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as 
nursing, include postdoctoral training and residency training if applicable. Add/delete rows as 
necessary.) 
INSTITUTION AND LOCATION 
DEGREE 
(if 
applicable) 
 
Completion 
Date 
MM/YYYY 
 
FIELD OF STUDY 
 
Tongji Medical University, Wuhan, 
China 
MD 
08/84 
Medicine 
Tongji Medical University, Wuhan, 
China 
MSc 
07/87 
Clinical Investigation 
Karolinska Institute, Stockholm, 
Sweden 
PhD 
04/98 
Cell & Molecular 
Physiology 
SUNY Downstate, NY 
Residency 
06/09 
Pediatrics 
Yale University, CT 
Fellow 
06/12 
Pediatric Gastroenterology 
 
A. Personal Statement 
 
This project proposes to test efficacy of calcium-ORS in reducing acute infectious diarrhea. It builds 
logically on my prior work and expertise. It is the extension of the work proposed in my K08 and R41 
awards and NASPGHAN foundation grant. When completed, this research may help develop a new oral 
rehydrating therapy for diarrhea in children. I have the skills and knowledge necessary to successfully 
carry out the proposed work. I am board-certified pediatrician and pediatric specialist in 
gastroenterology, hepatology and nutrition. I also have a broad background in physiology, with specific 
training and expertise in ion transport physiology. I used to be a renal physiologist. In 2000, I 
“transplanted” the knowledge and skills from renal into GI and initiated the current intestinal CaSR 
(calcium-sensing receptor)-diarrhea project (Cheng et al, AJP'02; Cheng et al, Gastroenterology'04; 
Geibel et al, PNAS'06). In 2012, I moved to UF and identified this unusual ‘all-inclusive’ antidiarrheal 
mechanism in the gut (Cheng, World J Gastro’16; Owen et al, Semin Cell Dev Biol’16; Tang et al, 
Front Physiol’16; Tang et al, Sci Rep’18). As a physician scientist, I wish to continue to transform 
result from bench into bedside. This current proposal represents one such effort. As a matter of fact, I 
have started in 2009 the conception of the Ca/CaSR-based antidiarrheal ORS with Dr. George Fuchs @ 
College of Public Health, University of Kentucky and Dr. Shafiqul Sarker in ICDDRB, Dhaka, 
Bangladesh. Thus, following the completion of proof of concept preclinical studies in vitro and in 
animal models, we decided to move on and do clinical trials on this in human patients with diarrhea in 
ICDDRB. ICDDRB is selected because it is the international diarrheal study center, the center that has 
played a major role in the discovery and implementation of ORS for the treatment of diarrhea. This 
combination of expertise will ensure the success of the project. University of Florida has its tradition for 
translational research and is home to Gatorade; the ultimate goal of this research is to generate a new 
Gatorade-like inexpensive but therapeutically active drink for people with diarrhea.  
 

B. Positions and Honors 
 
Positions and Employment 
1989-1991: Pediatrician, Tongji Hospital, Tongji Medical University, China 
1991-1992: W.H.O. Fellow, Pediatrics, Great Ormond Street Hospital for Children, London, UK 
1992-1993: Visiting Physician Scholar, St. Gorans Childrens Hospital, Karolinska Institute, Sweden. 
1999-2000: Postdoc Research Fellow, Vanderbilt University Medical Center, Nashville, TN 
2000-2007: Associate Research Scientist, Department of Physiology, Yale University, New Haven, CT. 
2012-2020: Assistant Professor, Department of Pediatrics, University of Florida, Gainesville, FL 
2020-present: Associate Professor, Department of Pediatrics, University of Florida, Gainesville, FL 
 
Other Experience and Professional Memberships 
1999     
 
Ad Hoc Reviewer, Pediatric Research 
2000     
 
Ad Hoc Reviewer, American Journal of Physiology-Renal Physiology 
2001-      
 
Member, American Gastroenterology Association 
2006   
 
Ad Hoc Reviewer, Renal Failure 
2012-   
 
Reviewer, Journal of Pediatric Gastroenterology and Nutrition 
2013-   
 
Reviewer, World Journal of Gastroenterology 
2013-   
 
Reviewer, Inflammatory Bowel Disease 
2013-   
 
Member, Editorial Board of World Journal of Experimental Medicine 
2007-       
 
Member of American Academy of Pediatrics 
2009-                          Member, North America Society of Pediatric Gastroenterology, Hepatology                         
                                    and Nutrition (NASPGHAN) 
2011-   
 
Member, Research Committee, NASPGHAN 
2013-   
 
Member, American College of Gastroenterology 
2014-   
 
Reviewer, Cell Communication and Signaling  
2015-   
 
Reviewer, PLOS One, BMC Med Genet, FESEB J 
2018-   
 
Member, Editorial Board of World Journal of Gastroenterology 
2019-   
 
Member, Editorial Board of Physiological Report 
 
Honors 
1991  
 
World Health Organization Award, London, UK 
1992     
 
Wenner-Gren Scholar, Stockholm, Sweden 
1997     
 
Sven & Ruth Nydahls Award, Stockholm, Sweden 
1997     
 
Ruth Lundells Award, Stockholm, Sweden 
1997     
 
Invited Lectureship, 14th International Congress of Nephrology,  
                                   Sydney, Australia  
2011 
Fellow to Faculty Transition Award in Inflammatory Bowel Disease, the North 
American Society of Pediatric Gastroenterology, Hepatology, and Nutrition 
Foundation 
2011 
Travel Award to the Single Topic Symposium "Effective Pediatric Clinical Trials 
in Gastrointestinal, Hepatobiliary and Pancreatic Disease and Nutrition”, New 
Orleans, 2011, NASPGHAN Foundation 
2012 
Travel Award to the Single Topic Symposium “Discovering the Future of 
Pediatric Inflammatory Bowel Disease”, Salt Lake City, 2012, NASPGHAN 
Foundation 
2012 
Travel Award for the World Congress of Pediatric, Gastroenterology, Hepatology 
and Nutrition in Taiwan, Taipei, Taiwan, 2012, NASPGHAN Foundation 

2012 
Distinguished Presentation Award, the 4th World Congress of Pediatric, 
Gastroenterology, Hepatology and Nutrition in Taiwan, Taipei, Taiwan, 2012, 
FISPGHAN 
2012     
Invited Lectureship, 4th World Congress of Pediatric, Gastroenterology, 
Hepatology and Nutrition in Taiwan, Taipei 
2013     
Invited Lectureship, NASPGHAN annual Meeting, Chicago 
2014 
NIH K08 Clinical Scientist Career Development Award, National Institutes of 
Health NICHD 
2015     
Invited Plenary Lectureship, 2nd International CaSR Symposium, American 
Society for Bone and Mineral Research, San Diego, CA 
2016     
Travel Award and Invited Lectureship, 5th World Congress of Pediatric, 
Gastroenterology, Hepatology and Nutrition in Montreal, Canada, FISPGHAN 
2017     
Invited Plenary Lectureship, 3rd International CaSR Symposium, Florence, Italy 
2020     
Invited Plenary Lectureship, 4th International CaSR Symposium, San Francisco, 
CA 
2021 
Invited Lectureship, American Society of Nephrology, San Diego, CA 
 
C. Contributions to Science  
 
1. Molecular model for bi-directional control of Na,K-ATPase activity by hormones in kidney 
 
• *Fisone G, *Cheng SX-J, Nairn AC, Czernik AJ, Hemmings HC Jr, Höög J-O, Bertorello AM, 
Kaiser R, Bergman T, Jörnvall H, Aperia A & Greengard P (1994). Identification of the 
phosphorylation site for cAMP-dependent protein kinase on Na+,K+-ATPase and effects of site-
directed mutagenesis. (*Shared 1st authorship) J Biol Chem 269: 9368-9373. 
• Cheng XJ, Fisone G, Aizman O, Aizman R, Levenson R, Greengard P & Aperia A (1997). PKA 
mediated phosphorylation and inhibition of Na+,K+-ATPase in response to beta-adrenergic 
hormone. Am J Physiol 42: C893-901. 
• Cheng X-J, Höög J-O, Nairn AC, Greengard P & Aperia A (1997). Regulation of rat Na+,K+-
ATPase activity by PKC is modulated by state of phosphorylation of Ser943 by PKA. Am J 
Physiol 273: C1981-C1986. 
• Nowicki S, Chen SL, Aizman O, Cheng X-J, Li D, Nowicki C, Nairn AC, Greengard P & Aperia 
A (1997). 20-Hydroxyeicosa-tetraenoic acid (20 HETE) activates protein kinase C. Role in 
regulation of rat renal Na+,K+-ATPase. J Clin Invest 99: 1224-1230. 
2.  Ion transport and salt-sensing by renal proximal tubules 
• Cheng SXJ, Aizman O, Nairn A, Greengard P & Aperia A (1999).  [Ca2+]i determines the 
effects of protein kinases A and C on activity of rat renal Na+,K+-ATPase. J Physiol   518: 37-
46. 
• Ibarra F, Cheng SX-J, Agren M, Svensson L-B & Aperia A (2002). Intracellular sodium can act 
as a signal for Na/K-ATPase phosphorylation / dephosphorylation in renal epithelial cells. Acta 
Physiol Scand 175 (2): 165-171. 
• Bertuccio CA, Cheng SX, Arrizurieta EE, Martín RS & Ibarra FR (2003). Mechanisms of Na-K-
ATPase phosphorylation by PKC in the medullary thick ascending limb of Henle in the rat. 
Pfluger’s Arch. 447(1):87-96. 
3. Discovery of a new receptor mechanism that controls intestinal fluid movement 

• Cheng SX, Okuda M, Hall AE, Geibel JP & Hebert SC (2002). Expression of calcium/nutrient-
sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion. Am J 
Physiol 283: G240-G250 
• Cheng SX, Geibel JP & Hebert SC (2004). Extracellular polyamines regulate fluid secretion in 
rat colonic crypts via the extracellular calcium-sensing receptor. Gastroenterology 126(1):148-
58. 
• Geibel J, Sritharan K, Geibel R, Geibel P, Persing JS, Seeger A, Roepke TK, Deichstetter M, 
Prinz C, Cheng SX, Martin D & Hebert SC (2006). Calcium-sensing receptor abrogates 
secretagogue-induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide 
destruction. PNAS USA, 103: 9390-7. 
 
• Ring A*, Cheng SX*, Kahle KT, Leng Q, Rinehart J, Lalioti MD, Volkman HM, Wilson FH, 
Hebert SC & Lifton RP (2007). WNK4 regulates activity of the epithelial Na channel in vitro and 
in vivo. PNAS USA, 104:4020-4. * shared 1st authorship 
 
4. Identification of CaSR as the 1st inclusive antidiarrheal mechanism in the gut 
• Cheng SX (2012). Calcium-sensing receptor inhibits secretagogue-induced electrolyte secretion 
by intestine via the enteric nervous system. Am J Physiol 303: G60-70 
• Cheng SX, Lightfoot YL, Yang T, Zadeh M, Tang L, Sahay B, Wang GP, Owen JL & 
Mohamadzadeh M (2014). Epithelial CaSR Deficiency Alters Intestinal Integrity and Promotes 
Proinflammatory Immune Responses. FEBS Lett. 588(22):4158-66. 
• Tang L, Peng M, Liu L, Chang W, Binder HJ & Cheng SX (2015). Calcium-Sensing Receptor 
Stimulates Cl-- and SCFA-dependent but Inhibits cAMP-dependent HCO3- Secretion in Colon.  
Am J Physiol.  308(10):G874-83  
• Owen JL, Cheng SX, Sahay B and Mohamadzadeh M (2016). The Role of the Calcium-Sensing 
Receptor in Gastrointestinal Inflammation. Semin Cell Dev Biol  49:44-51. 
• Cheng SX (2016). Calcium-sensing receptor: a new target for therapy of diarrhea. World J 
Gastro 22(9):2711-24.  
• Tang L, Cheng CY, Sun X, Pedicone AJ, Mohamadzadeth M and Cheng SX (2016). The 
Extracellular Calcium-Sensing Receptor in the Intestine: Evidence for Regulation of Colonic 
Absorption, 
Secretion, 
Motility, 
and 
Immunity. 
Front. 
Physiol. 
7:245. 
doi: 
10.3389/fphys.2016.00245 
• Tang L, Fang X, Winesett SP, Cheng CY, Binder HJ, Rivkees SA & Cheng SX (2017). 
Bumetanide increases Cl--dependent short-circuit current in late distal colon: evidence for the 
presence of active electrogenic Cl- absorption. PLOS ONE 12(2):e0171045 
• Sun X, Tang L, Winesett S, Chang W & Cheng SX (2018). Calcimimetic R568 inhibits 
tetrodotoxin-sensitive colonic electrolyte secretion and reduces c-fos expression in myenteric 
neurons. Life Sci 194:49-58. doi: 10.1016/j.lfs.2017.12.019 
• Tang L, Jiang L, McIntyre ME, Petrova E & Cheng SX (2018). Calcimimetic acts on enteric 
neuronal CaSR to reverse cholera toxin-induced intestinal electrolyte secretion. Sci Rep 
8(1):7851. doi: 10.1038/s41598-018-26171-4. 
 
 
D. Research Support 
Ongoing research Support 
None 
 
 

Completed Research Support 
Research Grant 
 
Cheng (PI) 
 
07/01/2012-06/30/2013 
NASPGHAN foundation 
The calcium-sensing receptor and nutritional therapy of IBD in children 
The specific aims of this proposal are designed to assess the role of the CaSR as a mechanism in 
mediating known nutritional therapy of inflammatory bowel disease (IBD) in children and to identify 
CaSR as a potential new target for pharmaco-nutritional therapy for IBD. 
Role: PI 
 
K08 HD079674 
 
Cheng (PI) 
 
04/10/2014-03/31/2020 
NIH/NICHD 
Calcium receptor action in childhood diarrhea 
The specific aims of this proposal are designed to understand the molecular and cellular mechanisms by 
which CaSR acts as an anti-diarrheal in the gut. 
Role: PI 
 
R41 HD092133 
 
Cheng (PI) 
 
04/01/2017-03/31/2019 
NIH/NICHD 
Development of CaSR nutrient therapy for childhood diarrhea  
The goal of this proposal is to use animal models of infectious diarrhea to test anti-diarrheal efficacy 
and safety of child-friendly, CaSR-activating nutrients. 
Role: PI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

CURRICULUM VITAE 
(September 2022) 
 
GEORGE J. FUCHS, III, M.D. 
Personal Information: 
 
 
Office Address: 
 
University of Kentucky College of Medicine 
 
 
 
 
Department of Pediatrics  
 
 
 
 
 
138 Leader Ave, Office 209 
 
 
 
 
 
Lexington, KY  40506  
 
 
 
Tel: (859) 218-1676 
 
 
 
 
Fax: (859) 257-7799 or (413) 793-1376 
 
 
 
 
 
E-mail: gjfuchs@usa.net; george.fuchs@uky.edu 
 
 
Education: 
 
1970-1974 
 
 
University of Missouri-Columbia, Columbia, Missouri 65212 
 
 
 
 
 
Degree:  BA Zoology 
1975-1976 
Universidad Autónoma de Guadalajara, School of Medicine 
 
 
 
 
Guadalajara, Mexico 
 
1977-1980 
 
 
University of Missouri-Columbia, School of Medicine 
 
 
 
 
 
Columbia, Missouri 65212, Degree:  M.D. 
 
Clinical Training: 
   Internship 
   July - December, 1980 
  
Internal Medicine, Department of Internal Medicine 
 
 
 
 
 
Good Samaritan Hospital, Phoenix, Arizona 85062 
   January - June, 1981      
 
Pediatrics, Department of Pediatrics 
 
 
 
 
 
Phoenix Hospitals Affiliated Pediatric Program, Arizona 85062, 
Residency 
   July, 1981 - June, 1983             
Pediatrics, Tufts-New England Medical Center, Boston Floating                   
                                                                       Hospital for Infants and Children,Boston, Massachusetts  02111 
Clinical/Research Fellowships: 
   July, 1983 - June, 1984                          Divisions of Geographic Medicine and Pediatric               
                                                                      Gastroenterology/Nutrition, Tufts-New England Medical Center 
 
 
 
 
 
Boston, Massachusetts 02111 
  July, 1984 - June, 1985  
  
Pediatric Infectious Diseases, University of Texas Health Science 
 
 
 
 
 
Center at Houston,Houston, Texas  77225 
  July, 1985 - June, 1986  
 
Pediatric Gastroenterology/Nutrition, University of Texas Health   
                                                                       Science, Center at Houston, Houston, Texas 77225 
 
Professional Background:  
 
Academic Appointments 
  2015 – Present: Professor of Pediatrics (with tenure), University of Kentucky College of Medicine                         
  2016 – Present: Professor, Department of Epidemiology, University of Kentucky College of Public Health       
  2016 – Present: Professor, Department of Preventive Medicine, and Environmental Health, University   
                                of Kentucky College of Public Health                                                                                                      
  2002 – 2015:        Professor of Health Policy and Management, Faye W. Boozman College of Public   
                                  Health, University of Arkansas for Medical Sciences                                             

  2001 – 2015:        Professor of Pediatrics (with tenure), College of Medicine, University of Arkansas    
                                for Medical Sciences 
  1998 – 2001:        Professor of Pediatrics (with tenure), Louisiana State University, School of   Medicine                        
                                in New Orleans 
   1992 - 1998:         Associate Professor of Pediatrics (with tenure), Louisiana State University  
 
                     School of Medicine in New Orleans 
   1986 - 1992    Assistant Professor of Pediatrics, Louisiana State University School of Medicine in New           
                               Orleans 
 
Other Professional Positions (last 7 years): 
 
2019 – 2022 
Senior Ambulatory Medical Director for Pediatrics, UK HealthCare, Kentucky Children’s Hospital 
2017 - 2022 
Vice Chair for Clinical Affairs, Dept. of Pediatrics, University of Kentucky College of Medicine 
2015 - 2022 
Chief, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics 
 
 
University of Kentucky College of Medicine 
2017 – Present: Member, Primary Care Provider Association Advisory Board,  Academy of Nutrition and Dietetics 
2017 – Present:  Member, Committee on Nutrition, American Academy of Pediatrics 
2013 - Present :  Adjunct Scientist, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)  
2013 – 2018:       Member, Gastroenterology & GI Surgery Working Group, (annually through 2018) US News and   
                               World Report Best Children's Hospitals project 
2013 – present: Editor, Nutrition and Metabolism Section of the Journal of Translational Medicine (JTM) 
2011 – 2020:      Editorial Board, Journal of Pediatric Gastroenterology  and Nutrition 
2015 – 2016:      Member, Expert Committee, NIAID Food Allergy Clinical Guidelines update. National Institutes  
                             of Health (NIH) 
 Society Memberships:  
 
• 
North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition 1986 - Present 
• 
Infectious Disease Society of America 1986 - Present 
• 
American Academy of Pediatrics 1987 - Present 
• 
American Gastroenterological Association 1989 - Present 
• 
American Society for Nutrition 1994 – Present 
• 
Global Nutrition Council 1994 - Present 
 
 
 
 
Grants and Contracts (last 5 years): 
 
1. Funding entity: 
Unicef 
 
Title of project: 
Effectiveness trial of day-care versus usual care management 
of severe pneumonia and malnutrition in children using  
a health system approach”. 
 
Dates:   
 
2015-2018 
 
Amount: 
 
$1,500,000 
 
Role: 
 
 
Co-P.I. (External P.I.) 
 
2. Funding entity:  
Unicef 
 
Title of project: Effectiveness trial of day-care versus usual care management 
of severe pneumonia with or without malnutrition in children using  
the health system of Bangladesh”.  Expansion proposal 

 
Dates:   
 
2017-2019 
 
Amount: 
 
$897,499 
 
Role: 
 
 
Co-P.I. (External P.I.) 
 
3. Funding entity:  
Botnar Foundation 
 
Title of project: Effectiveness trial of day-care versus usual care management 
of severe pneumonia with or without malnutrition in children using  
the health system of Bangladesh”.   
 
Dates:   
 
2017-2019 
 
Amount: 
 
$602,192 
 
Role: 
 
 
Co-P.I. (External P.I.) 
 
4. Funding entity:  
Biomarin 
 
Title of project: An Open-label Extension Study to Evaluate the Safety and Efficacy 
of Subcutaneous Injections of Pegvaliase (> 40 mg/day Dose) in  
Adults with Phenylketonuria”.   
 
Dates:   
 
2018-2021 
 
Amount: 
 
$98,976 
 
Role: 
 
 
Site P.I. 
 
5. Funding entity:  
UBS Optimus Foundation 
 
Title of project: Proposal for Expansion Phase II “Analysis and Dissemination”, 
 
 
 
 
Effectiveness trial of day-care versus usual care management 
 
 
 
 
of severe pneumonia and malnutrition in children using  
 
 
 
 
a health system approach”. 
 
Dates:   
 
2019 
 
Amount: 
 
$142,000 
 
Role: 
 
 
Co-P.I. (External P.I.) 
 
6. Funding entity:  
ModernaTx, Inc. 
 Title of project: A Phase 2/3, Two-Part, Open-Label, Dose Escalation, Age De-escalation 
  
 
 
and Randomized, Observer-Blind, Placebo-Controlled Expansion Study 
  
 
 
to Evaluate the Safety, Tolerability, Reactogenicity, and Effectiveness of  
  
 
 
mRNA-1273 SARS-CoV-2 Vaccine in Healthy Children 6 months to  
  
 
 
< 12 Years of Age. 
Dates:  
 
2021-23 
Amount: 
 
$2,255,362 
Role: 
 
 
Site P.I. 
 
7. Funding entity:  
ModernaTx, Inc. 
 Title of project: COVID-19: ROVER-An Open-Label, Phase 3 Study to Evaluate the Safety  
  
 
 
and Immunogenicity of the mRNA-1273.214 Vaccine for SARS-CoV-2  
  
 
 
Variants of Concern in Participants Aged 6 Months to < 6 Years 
 Dates:  
 
2022-24 
Amount: 
 
$330,332 
Role: 
 
 
Site P.I. 
Bibliography (last 5 years): 
 

1. 
Togias A, Cooper SF, Acebal M, Assa'ad A, Baker JR, Beck LA, Block J, Byrd-Bredbenner C, Chan ES, 
Eichenfield LF, Fleischer DM, Fuchs GJ, Furuta GT, Greenhawt MJ, Gupta RS, Habich M, Jone SM, Keaton, 
K, Muraro A, Plaut MS, Rosenwasser, LJ, Rotrosen D, Sampson HA, Schneider LC, Sicherer SH, Sidbury R, 
Spergal J, Stukus DR, Venter C, Boyce JA.  Addendum Guidelines for the Prevention of Peanut Allergy in 
the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert 
Panel.  J Allergy Clin Immunol. 2017;139:29-44. 
 
• Togias A, Cooper SF, Acebal M, Assa'ad A, Baker JR, Beck LA, Block J, Byrd-Bredbenner C, Chan ES, 
Eichenfield LF, Fleischer DM, Fuchs GJ, Furuta GT, Greenhawt MJ, Gupta RS, Habich M, Jone SM, Keaton, 
K, Muraro A, Plaut MS, Rosenwasser, LJ, Rotrosen D, Sampson HA, Schneider LC, Sicherer SH, Sidbury R, 
Spergal J, Stukus DR, Venter C, Boyce JA.  Addendum Guidelines for the Prevention of Peanut Allergy in 
the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert 
Panel.  J Pediatr Nurs 2017;32:91-98. 
 
• Togias A, Cooper SF, Acebal M, Assa'ad A, Baker JR, Beck LA, Block J, Byrd-Bredbenner C, Chan ES, 
Eichenfield LF, Fleischer DM, Fuchs GJ, Furuta GT, Greenhawt MJ, Gupta RS, Habich M, Jone SM, Keaton, 
K, Muraro A, Plaut MS, Rosenwasser, LJ, Rotrosen D, Sampson HA, Schneider LC, Sicherer SH, Sidbury R, 
Spergal J, Stukus DR, Venter C, Boyce JA.  Addendum Guidelines for the Prevention of Peanut Allergy in 
the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert 
Panel.  Pediatr Dermatol. 2017;34(1):e1-e21. 
 
• Togias A, Cooper SF, Acebal M, Assa'ad A, Baker JR, Beck LA, Block J, Byrd-Bredbenner C, Chan ES, 
Eichenfield LF, Fleischer DM, Fuchs GJ, Furuta GT, Greenhawt MJ, Gupta RS, Habich M, Jone SM, Keaton, 
K, Muraro A, Plaut MS, Rosenwasser, LJ, Rotrosen D, Sampson HA, Schneider LC, Sicherer SH, Sidbury R, 
Spergal J, Stukus DR, Venter C, Boyce JA.  Addendum Guidelines for the Prevention of Peanut Allergy in 
the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert 
Panel.  Ann Allergy Asthma Immunol 2017;118:166-73. 
 
• Togias A, Cooper SF, Acebal M, Assa'ad A, Baker JR, Beck LA, Block J, Byrd-Bredbenner C, Chan ES, 
Eichenfield LF, Fleischer DM, Fuchs GJ, Furuta GT, Greenhawt MJ, Gupta RS, Habich M, Jone SM, Keaton, 
K, Muraro A, Plaut MS, Rosenwasser, LJ, Rotrosen D, Sampson HA, Schneider LC, Sicherer SH, Sidbury R, 
Spergal J, Stukus DR, Venter C, Boyce JA.  Addendum Guidelines for the Prevention of Peanut Allergy in 
the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert 
Panel.  J Acad Nutr Diet 2017;117:788-93. 
 
• Togias A, Cooper SF, Acebal M, Assa'ad A, Baker JR, Beck LA, Block J, Byrd-Bredbenner C, Chan ES, 
Eichenfield LF, Fleischer DM, Fuchs GJ, Furuta GT, Greenhawt MJ, Gupta RS, Habich M, Jone SM, Keaton, 
K, Muraro A, Plaut MS, Rosenwasser, LJ, Rotrosen D, Sampson HA, Schneider LC, Sicherer SH, Sidbury R, 
Spergal J, Stukus DR, Venter C, Boyce JA.  Addendum Guidelines for the Prevention of Peanut Allergy in 
the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert 
Panel.  JAAPA 2017;30:1-5. 
 
2. 
Das SK, Chisti MJ, Sarker MHR, Das J, Ahmed S, Shahunja KM, Nahar S, Gibbons N, Ahmed T, Faruque ASG, 
Rahman M, Fuchs GJ, Mamun AA, Baker PJ.  Long-term impact of changing childhood malnutrition on 
rotavirus diarrhoea: two decades of adjusted association with climate and socio-demographic factors 
from urban Bangladesh.  PlOS ONE 2017;12:e0179418. 
 
3. 
Fuchs GJ.  The future of the discipline of infectious diseases. (letter) Clin Infect Dis 2017;65:1597-98. 
 
4. 
Fuchs GJ.  Imported infant formula not reviewed by FDA may pose health risks.  AAP News 2018;39:12. 

 
5. 
Fuchs GJ.  Efficacy of reslizumab for eosinophilic esophagitis.  (letter) JPGN 2018;67:E86.  
 
6. 
Ofei SY, Fuchs GJ:  Constipation burden in children with autism spectrum disorder: emergency 
department and healthcare use.  J Pediatr 2018;202:12-13. 
 
7. 
Ashraf H, Alam NH, Sultana M, Jahan SA, Begum N, Farzana S, Chisti MJ, Kamal M, Shamsuzzaman A,  
Ahmed T, Khan JAM, Fuchs GJ, Duke T, Gyr N.  Day clinic vs. hospital care of pneumonia and severe 
malnutrition in children under five: a randomised trial.  Trop Med Int Health. 2019;24:922-31.   
doi: 
10.1111/tmi.13242  
 
8. 
Ofei SY, Fuchs GJ.   Gastroenterology.  In: Handbook of Interdisciplinary Treatments for Autism Spectrum 
Disorder.  R. D. Rieske (ed.).  Springer Nature Switzerland AG 2019. Pp297-307. 
 
9. 
Greer FR, Sicherer SH, Burks AW; Committee on Nutrition; Section on Allergy and Immunology. The 
Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: 
The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of 
Introduction of Allergenic Complementary Foods. Pediatrics 2019 Apr;143(4):e20190281. doi: 
10.1542/peds.2019-0281. Epub 2019 Mar 18. PMID: 30886111. 
 
10. 
Muth ND, Dietz WH, Magge SN, Johnson RK, American Academy of Pediatrics; Section on Obesity; 
Committee on Nutrition; American Heart Association. Public Policies to Reduce Sugary Drink 
Consumption in Children and Adolescents. Pediatrics. 2019 Apr;143(4). pii: e20190282. PMID: 30910915. 
 
11. 
Bernstein AS, Oken E, de Ferranti S, AAP COUNCIL ON ENVIRONMENTAL HEALTH, AAP COMMITTEE ON 
NUTRITION. Fish, Shellfish, and Children’s Health: An Assessment of Benefits, Risks, and Sustainability. 
Pediatrics. 2019;143(6): e20190999. 
 
12. 
Bray AE, Ahmed S, Das SK, Khan SH, Christi MJ, Faruque ASG, Ahmed T, Fuchs GJ.  Viral pathogen-specific 
clinical and demographic characteristics of children with moderate-to-severe diarrhea in rural 
Bangladesh.  Am J Trop Med Hyg 2019;101:304-9. 
 
13. 
Baker-Smith CM, de Ferranti SD, Cochran WJ; Committee on Nutrition; Section on Gastroenterology, 
Hepatology, and Nutrition.  The Use of Nonnutritive Sweeteners in Children.  Pediatrics 2019 Nov;144(5). 
pii: e20192765. doi: 10.1542/peds.2019-2765. 
 
14. 
American Academy of Pediatrics Committee on Nutrition.  Pediatric Nutrition (“Yellow Book”).  
Kleinman RE and Greer FR (eds).  8th ed. Itasca, IL: American Academy of Pediatrics; 2019. 
 
15. 
Fuchs GJ, contributor, Pediatric Nutrition (“Yellow Book”).  Kleinman RE and Greer FR (eds).  8th ed. 
Itasca, IL: American Academy of Pediatrics; 2019. 
 
16. 
Ofei SY, Fuchs GJ.  Principles and Practice of Oral Rehydration.  Curr Gastroenterol Rep. 2019;7;21:67-72.  
doi: 10.1007/s11894-019-0734-1. 
 
17. 
Fuchs 
GJ. 
 
Is 
it 
OK 
to 
buy 
imported 
formulas 
online? 
 
AAP, 
healthychildren.org, 
https://www.healthychildren.org/English/tips-tools/ask-the-pediatrician/Pages/Is-it-OK-to-buy-
imported-formulas-online.aspx, Feb 26, 2020. 
 

18. 
Preliminary Technical Report: The Martin County Kentucky Community-Engaged Drinking Water Health 
Pilot Study.  Unrine, JM, Sanderson WT, Christian WJ, Pennell K, Ormsbee L, Hoover A, Fuchs GJ. 2020. 
 
19. 
Coauthor. Referrals to a Registered Dietitian Nutritionist Primary Care Provider Toolkit.  Academy of 
Nutrition and Dietetics, 2020. https://www.eatrightpro.org/payment/getting-started/referrals-and-
primary-care-partnership/referrals-to-a-registered-dietitian-nutritionist-primary-care-provider-toolkit  
 
20. 
Chowdhury F, Bin Shahid ASMS, Tabassum M, Parvin I, Ghosh PK, Hossain MI, Alalm NH, Faruque ASG, 
Huq S, Shahrin L, Homaira N, Hassan Z, Akhtar Z, Mah-E-Muneer S, Fuchs GJ, Ahmed T, Chisti MJ.  
Vitamin D supplementation among Bangladeshi children under-five years of age hospitalised for severe 
pneumonia: 
a 
randomised 
placebo 
controlled 
trial. 
 
PLoS 
One 
2021;16:e0246460. 
doi: 
10.1371/journal.pone.0246460.  
 
21. 
Sultana M, Alam NH, Faruque ASG, Fuchs GJ, Gyr N, Chisti MJ, Duke T, Ahmed T, Gold L. Household 
economic burden of childhood severe pneumonia in Bangladesh: A cost-of-illness study.  Arch Dis Child 
2021;106:539-546. 
 
22. 
Parker MG, Stellwagen LM, Noble L, et al; AAP Section on Breastfeeding, Committee on Nutrition, 
Committee on Fetus and Newborn. Promoting Human Milk and Breastfeeding for the Very Low Birth 
Weight Infant. Pediatrics. 2021;148(5):e2021054272.  
 
23. 
Kamal I. A. Chowdhury KIA, Jabeen I, Rahman M, Faruque ASG, Alam NH, Ahmed T, Fuchs GJ, Duke T, Gyr 
N, Sarma H.  Barriers to seeking timely treatment for severe childhood pneumonia in rural Bangladesh.  
Arch Dis Child 2022;107:436-440. 
 
24. 
Radulescu A, Dugan AJ, Killian M, Attia S, Mouzaki M, Fuchs G, Kohli R, Bada H, Kern P, Softic S.  
Stratification by obesity class rather than age, can identify a higher percent of children at risk for non-
alcoholic fatty liver disease and metabolic dysfunction.  
Pediatr Obes 2022;17:e12862. 
https://doi.org/10.1111/ijpo.12862. 
 
25. 
Ofei SY and Fuchs GJ.  Fluid and electrolytes.  In: Pediatric Nutrition in Practice.  Koletzko B, Bhutta ZA, 
Dhansay MA, Makrides M, Orsi M, Cai W, Duggan CP (eds): Pediatric Nutrition in Practice. 3rd Edition. 
Ofei SY, Fuchs GJ. 1.3.6 Fluid and Electrolytes. World Rev Nutr Diet. 2022;124:75-80. doi: 
10.1159/000516731. Epub 2022 Mar 3. PMID: 35240630. 
 
26. 
Brar S, Haugh C, Robertson N, Owuor PM, Waterman C, Fuchs GJ, Attia SL.  The impact of Moringa 
oleifera leaf supplementation on human and animal nutrition, growth, and milk production: A systematic 
review.  Phytotherapy Research 2022;1600–15. 
 
27. 
Nasrin S, Tariqujjaman Md, Sultana M, Zaman RA, Shahjahan A, Chisti MJ, Faruque ASG, Ahmed T, Fuchs 
GJ, Gyr N, Alam NH.   Factors associated with community acquired severe pneumonia in under five 
children in Dhaka, Bangladesh: a case control analysis.  PLOS One 2022 Mar 23;17(3):e0265871. doi: 
10.1371/journal.pone.0265871. PMID: 35320317. 
 
28. 
Hand I, Noble L, Abrams SA; AAP Committee on Fetus and Newborn, Section on Breastfeeding, 
Committee on Nutrition. Vitamin K and the Newborn Infant. Pediatrics 2022; 149: 58-61.    
2022;149(3):e2021056036  
 
29. 
Creech CB, Anderson E, Berthaud V, Yildirim I, Atz AM, Melendez Baez I, Finkelstein D, Pickrell P, Kirstein 
J, Yut C, Blair R, Clifford RA, Dunn M, Campbell JD, Montefiori DC, Tomassini JE, Zhao X, Deng W, Zhou H, 

Ramirez Schrempp D, Hautzinger K, Girard B, Slobod K, McPhee R, Pajon R, Das R, Miller JM, Schnyder 
Ghamloush S; KidCOVE Study Group. Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 
Years of Age. N Engl J Med. 2022;386:2011-23. 
• Largest pediatric mRNA vaccine trial conducted to date (as of June 2022). 
• Basis for emergency use authorization for mRNA-1273 (COVID-19 vaccine) in children age 6 months 
to 11 years. 
 
30. 
Murphy MO, Lee TM, Ryzowicz TA, Fuchs GJ.  Restricted Diets.  In: Pediatric Nutrition for Dietitians.  
Goday PS, Walia CLS (eds).  CRC Press, Boca Raton 2022.  ISBN 9780367705046 
 
31. 
Mogaka JN, Owuor PM, Odhiambo Silvia, Waterman C, McGuire MK, Fuchs GJ, Attia SL.  Investigating the 
Impact of Moringa oleifera Supplemented to Kenyan Breastfeeding Mothers on Maternal and Infant 
Health: A Cluster Randomized Single-Blinded Controlled Pilot Trial Protocol.  JPGN Reports (2022) 
3:3(e237). 
 
32. 
Anderson EJ, Creech B, Berthaud V, Piramzadian A,  Johnson KA, Zervos M, Garner F, Griffin C, 
Palanpurwala K, Turner M, Gerber J, Bennett RL, Ali K, Ampajwala M, Berman G, NayakJ, Chronis C, 
Rizzardi B, Muller W, SmithCA, Fuchs G, Hsia D, Tomassini JE, DeLucia D, Reuter C, Kuter B, Zhao X, Deng 
W, Zhou H, Ramirez Schrempp D, Hautzinger K, Girard B, Slobod K, McPhee R, Pajon R, Aunins A, Das R, 
Miller JM, Schnyder Ghamloush S, on behalf of the KidCOVE Study Group.  Evaluation of mRNA-1273 
Vaccine in Children 6 Months through 5 Years of Age.  New England Journal of Medicine (in press). 
 
Submitted/in preparation: 
 
1. 
Sultana M, Alam NH, Faruque ASG, Fuchs GJ, Gyr N, Chisti MJ, Duke T, Ahmed T, Gold L.  Economic 
evaluation alongside the cluster-randomised controlled trial of Day care versus Existing care 
management of severe childhood pneumonia with or without malnutrition in Bangladesh: study 
protocol.  Submitted 
 
2. 
Ali, S, Tariquzzaman M, Sultana M, Nasrin S, Chisti MJ, Alam NH, Ahmed T, Faruque ASG, Gyr N, Fuchs GJ.   
Incidence, case fatality, mortality, and healthcare-seeking behavior of children with severe pneumonia in 
rural Bangladesh. (in preparation). 
 
 
3. 
Alam NH, Faruque ASG, Ashraf H, Chisti MJ, Ahmed T, Sultana M, Zaman K, Ali S, Shahnawaz, Nasrin S, 
Tariqujjaman, Ehsan, Amin R, Mollah AH, Kabir L, Shahidullah, Khanam W, Islam K, Kim M, Duke T, Gyr N, 
Fuchs GJ.  Effectiveness, safety and economic viability of daycare versus usual care management of 
severe pneumonia with or without malnutrition in children within the existing health system of 
Bangladesh: a cluster randomized controlled trial.  (Submitted) 
 
4. 
AAP Clinical Report: Older Infant- Young Child Formulas. Fuchs GJ, Abrams S, Amevor A.  (in preparation) 
 
5. 
Haugh C, Attia S, Brar S, Robertson J, DiTommaso L, Fuchs G, Schadler A, Radulescu A, Attia SL.  
Cardiometabolic Risk Factors in South American Children: A Systematic Review and Meta-Analysis.  
(submitted) 
 
6. 
Sultana M, Watts JJ, Alam NH, Faruque ASG, Fuchs GJ, Gyr N, Ali N, Chisti MJ, Ahmed T, Abimanyi-Ochom 
J, Gold L.  Cost of childhood severe pneumonia management in selected health facilities in Bangladesh: a 
provider perspective. (submitted) 
 
 

BIOGRAPHICAL SKETCH 
NAME: Zhigang Li 
eRA COMMONS USER NAME (credential, e.g., agency login): ZHIGANGL 
POSITION TITLE: Associate Professor 
EDUCATION/TRAINING  
INSTITUTION AND LOCATION 
DEGREE 
(if 
applicable) 
 
Completion 
Date 
MM/YYYY 
 
FIELD OF STUDY 
 
Nankai University, Tianjin, China 
BS 
06/2001 
Mathematics 
Nankai University, Tianjin, China 
MS 
06/2004 
Probability theory 
Auburn University, Auburn, AL 
MPS 
08/2006 
Statistics 
Columbia University, New York, NY 
PHD 
10/2010 
Biostatistics 
A. Personal Statement 
I am a tenured associated professor in the Department of Biostatistics at the University of Florida. My research 
interests include microbiome data modeling, mediation data analysis, high-dimensional data analysis, generalized 
estimation equations, mixed-effect models and structural equation modeling (SEM). I am currently the PI of an 
NIH-funded R01 grant (R01GM123014) to study human microbiome mediating disease-leading causal pathways 
in children. I am also the PI of the Data Science Core of a P01 grant (P01AA029543) to evaluate interventions 
including a probiotic intervention to improve alcohol-related comorbidities along the gut-brain axis in persons 
with HIV infection. I was also a project PI of the molecular epidemiology center (P20GM104416) to investigate 
mediation effects of high-dimensional mediators. I was the PI of an R03 grant (2014-2016) from NIH to develop 
modeling approaches for jointly analyzing survival data and longitudinal quality of life (QOL) data in palliative 
care clinical trials. Prior to that, I was the contact-PI of a two-year pilot grant (2012-2014) from the NCI-
designated Norris Cotton Cancer Center to develop joint analysis models for survival data and longitudinal QOL 
data. Ongoing and recently completed projects that I would like to highlight are provided below: 
 
R01GM123014 (Li) 
                09/12/17-07/31/22     NCE                         
NIGMS                 
Mediation Analysis Methods to Model Human Microbiome Mediating Disease-Leading Causal  
Pathways in Children 
Role: PI 
 
P01AA029543 (Cook)                 9/10/2021-8/31/2026 
NIAAA                 
Interventions to improve alcohol-related comorbidities along the gut-brain axis in persons with HIV infection 
Role: PI of the Data Science Core 
 
U24AA029959 (Wu, Cook)        9/22/2021-8/31/2026 
NIAAA 
Southern HIV and Alcohol Research Consortium Biomedical Data Repository 
Role: co-I 
 
R01AG068128 (Armstrong) 
                7/1/2020-6/30/2025                              
NIDA                  
Identifying Factors Predicting ACcurately End-of-Life in Dementia with Lewy Bodies and Promoting Quality 
End-of-Life Experiences: the PACE-DLB Study 
Role: Co-I 
 

R01AG071729 (Wang)        2/15/2022-11/30/2026 
NIA 
Real-Time and Long-Term Effects of Medical Marijuana on Older Adults: A Prospective Cohort Study 
Role: co-I 
 
(El-Jawahri) 
                7/1/2018-6/30/2023                              
American Cancer Society – Research Scholar Grant 
                 
Randomized Trial of a multimodal sexual dysfunction intervention for hematopoietic stem cell transplant 
survivors 
Role: UF Subaward PI 
 
UG3DE030433 (Fillingim, Ribeiro-Dasilva)     7/1/2022- 6/30/2028 
NIDCR 
Photobiomodulation for the Management of Temporomandibular Disorder Pain 
Role: Co-I 
 
T32NS082168 (Bowers) 
                7/1/2020-6/30/2025                              
NINDS                  
Interdisciplinary Training in Movement Disorders and Neurorestoration 
Role: Co-I 
 
R21CA264927 (Jobin, El Haddad)     5/10/2022- 2/29/2024 
NCI 
Bacteriophage-mediated microbiota modification to prevent colorectal cancer development 
Role: Co-I 
Selected Completed Research Support 
R01DA042069 (Cook)               04/01/2019- 3/31/2021 
NIDA 
Alzheimer’s-gut-microbiome grant supplement for MAPLE 
Role: co-I 
  
B. Positions and Honors 
Positions and Employment 
08/2018-present 
Associate Professor (University Preeminence hire), Department of Biostatistics, College of 
Public Health & Health Professions, University of Florida, Gainesville, FL  
08/2018-present    Associate Member, UF Health Cancer Center, University of Florida, Gainesville, FL 
08/2018-present    Adjunct Associate Professor, Department of Epidemiology, Geisel School of Medicine at 
Dartmouth, Hanover, NH 
02/2018-7/2018 
Associate Professor, Department of Biomedical Data Science, Department of Epidemiology, 
Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, 
Hanover, NH 
2011-01/2018 
Member, Norris Cotton Cancer Center, NH 
2010-01/2018 
Assistant Professor, Department of Community and Family Medicine, Department of 
Biomedical Data Science (2015-2018), Department of Epidemiology (2017-2018), Geisel 
School of Medicine at Dartmouth College, Hanover, NH       
2007-2010 
Biostatistician, Columbia Center for Children's Environmental Health, Columbia University, 
New York, NY    
 
Other Experience and Professional Memberships 
2022 
Educational Advisory Committee, ENAR2023 conference 
07/2022 
Reviewer in NIH Special Emphasis Panel ZRG1 PSE-F(02) 
03/2022 
Reviewer in  NIH IRAP Study Section: Infectious Diseases, Reproductive Health, Asthma 
and Pulmonary Conditions 
07/2021 
Reviewer in NIH Study Section: NIH Special Emphasis Panel ZHL1  CSR-A (O2) 

01/2021 
Department of Defense DMDRP grant review panel  
07/2020 
Reviewer in  NIH Study Section: Special Emphasis Panel ZDK1 GRB-G (O4) 
02/2020 
Department of Defense PHP-2 grant review panel 
2019 
Department of Defense PSAAD grant review panel, DC 
2019 
Hitchcock foundation grant review, NH 
2019 
UF Health Cancer Center CPS_CTHR Collaborative Pilot Program, University of Florida, 
FL 
11/2018 
Reviewer in  NIH Study Section: Special Emphasis Panel ZHL1 CSR-R (F3) 
02/2018 
NIH ECHO Opportunities and Infrastructure Fund review panel 
04/2017 
The PRESTIGE post-doc fellowship program reviewer, Campus France 
05/2016,17 
Laura and John Arnold Foundation external reviewer, Houston, Texas 
08/2015,16 
Cancer Center Developmental Funds Review Panel, Norris Cotton Cancer Center, NH 
02/2019-present 
Associate editor: Surgery 
2013-2020 
Associate editor: Frontiers in Public Health 
2013- present 
Associate editor: BioData Mining  
2011- 2017 
Clinical Cancer Review Committee, Norris Cotton Cancer Center, NH 
2017- present 
Member, Association for the Advancement of Artificial Intelligence 
2017- present 
Member, American Public Health Association 
2011- present 
Member, International Chinese Statistical Association 
2010- present 
Member, Eastern North American Region/International Biometric Society 
2009- present 
Member, American Statistical Associations 
 
Honors 
2022 
Outstanding Student Support Award, Dept of Biostatistics, University of Florida, 
Gainesville, FL 
2019 
Outstanding Teaching Award, Dept of Biostatistics, University of Florida, 
Gainesville, FL 
2018-present 
University Preeminence Faculty Hire, University of Florida, Gainesville, FL 
2006-2010 
PhD student fellowship, Columbia University 
1996 
First Prize, Chinese National Mathematical Olympiad 
 
C. Contribution to Science (*corresponding author, #co-first author) 
1. 
Microbiome analysis.  
 
• Wu Q, O’Malley J, Datta S, GharaiBeh RZ, Jobin C, Coker M, Hoen AG, Christensen BC, Madan JC, 
Karagas MR, Li Z* (2022) MarZIC: A Marginal mediation model for Zero-Inflated Compositional 
mediators with applications to microbiome data. Genes Vol 13 Issue 6 
• Li Z*, Tian L, O'Malley J, Karagas MR, Hoen AG, Christensen BC, Madan JC, Wu Q, Gharaibeh RZ, Jobin 
C, Li H (2021) IFAA: Robust association identification and Inference For Absolute Abundance in 
microbiome analyses. Journal of the American Statistical Association 
• Jie Zhou, Weston D. Viles, Boran Lu, Zhigang Li, Juliette C. Madan, Margaret R. Karagas, Jiang Gui, Anne 
G. Hoen (2020) Identification of microbial interaction network: zero-inflated latent Ising model based 
approach. BioData Mining 
• Li Z*, Lee K, Karagas M, Madan J, Hoen A, O’Malley AJ and Li H (2018) Conditional regression based on 
a multivariate zero-inflated logistic normal model for modeling microbiome data. Statistics in Biosciences 
10(3):587-608. PMCID: PMC6432796 
• Modupe O. Coker, Hannah E. Laue, Anne G. Hoen, Margaret Hilliard, Erika Dade, Zhigang Li, Thomas 
Palys, Hilary G. Morrison, Emily Baker, Margaret R. Karagas and Juliette C. Madan (2021) Infant Feeding 
Alters the Longitudinal Impact of Birth Mode on the Development of the Gut Microbiota in the First Year of 
Life. Frontiers in Microbiology. https://doi.org/10.3389/fmicb.2021.642197 
• Coker MO, Hoen AG, Dade EF, Lundgren S, Li Z, Wong A, Zens MS, Palys T, Morrison HG, Sogin ML, 
Baker E, Karagas MR, Madan JC (2020) Specific class of intrapartum antibiotics relate to maturation of the 
infant gut microbiome: a prospective cohort study. BJOG: An International Journal of Obstetrics and 
Gynaecology 127(2):217-227 PMCID: PMC6803026 

• Yaohua Yang, Wei Zheng, Qiuyin Cai, Martha J. Shrubsole, Zhiheng Pei, Robert Brucker, Jennifer 
Sonderman, Mark Steinwandel, Seth R. Bordenstein, Zhigang Li, William J. Blot, Xiao-Ou Shu, Jirong 
Long (2019) Cigarette Smoking and Oral Microbiome in Low-income and African American Populations. 
Journal of Epidemiology & Community Health 
• Hoen A, Madan J, Li Z, Coker M, Lundgren S, Morrison H, Palys T, Jackson B, Sogin M, Cottingham K, 
Karagas M (2018) Sex-specific gut microbiome impacts of infant arsenic exposure in a US population. 
Scientific Reports 8 
 
2. 
Developing modeling approaches for analyzing survival data and longitudinal data. 
 
•  Li Z* and McKeague IW (2013) Power and sample size calculations for generalized estimating equations 
via local asymptotics. Statistica Sinica 23, 231-250 PMCID: PMC3903421 
• Li Z*, Tosteson TD and Bakitas M (2013) Joint modeling quality of life and survival using a terminal 
decline model in palliative care studies. Statistics in Medicine 32(8):1394-406 PMCID: PMC3623280 
• Li Z*, McKeague IW and Lumey LH (2014) Optimal design strategies for sibling studies with binary 
exposures. The International Journal of Biostatistics 10: 185-96 PMCID: PMC4412035 
• Li Z*, H. R. Frost, Tor Tosteson, Lihui Zhao, Lei Liu, Kathleen Lyons, Huaihou Chen, Bernard Cole, David 
Currow, Marie Bakitas (2017) A Semiparametric Joint Model for Terminal Trend of Quality of Life and 
Survival in Palliative Care Research. Statistics in Medicine 1 36(29):4692-4704 PMCID: PMC5698117 
 
3. 
Mediation analysis in children’s environmental health research  
 
• Gilbert-Diamond D, Li Z, Perry A, Spencer S, Gandolfi AJ and Karagas MR (2013) A population-based 
case–control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA. 
Environmental Health Perspectives. 121:1154-1260 PMCID: PMC3801199 
• Fei DL, Koestler DC, Li Z, Giambelli C, Sanchez-Mejias A, Gosse JA, Marsit CJ, Karagas MR and Robbins 
DJ (2013) Association between In Utero arsenic exposure, placental gene expression, and infant birth 
weight: a US birth cohort study. Environmental Health July 16; 12:58 PMCID: PMC3733767 
• Davis MA, Li Z, Gilbert-Diamond D, MacKenzie T, Cottingham KL, Jackson BP, Lee JS, Baker ER, Marsit 
CJ and Karagas MR (2014) Infant toenails as a biomarker of in utero arsenic exposure. Environmental 
Health 24(5): 467–473 PMCID: PMC4141012 
• Lesseur C, Armstrong DA, Paquette AG, Li Z, Padbury JF and Marsit CJ (2014) Maternal obesity and 
gestational diabetes are associated with placental leptin DNA methylation. The American Journal of 
Obstetrics & Gynecology 211(6):654. e1-9 PMCID: PMC4254188 
 
a) Mediation analysis in psychology and behavioral science.  
• Gibbons F, Roberts M, Gerrard M, Li Z, Beach S, Simons R, Weng C-Y and Philibert R (2012) The impact 
of stress on the life history strategies of African American adolescents: cognitions, genetic moderation, and 
the role of discrimination.  Developmental psychology 48: 722-739. PMCID: PMC4324554 
• O'Hara RE, Gibbons F, Gerrard M, Li Z and Sargent J (2012) Greater exposure to sexual content in popular 
movies predicts earlier sexual debut and increased sexual risk taking. Psychological Science 23(9):984-93 
PMCID: PMC3779897  
• O'Hara RE, Gibbons FX, Li Z, Gerrard M & Sargent J (2013). Specificity of early movie effects on 
adolescent sexual behavior and alcohol use.  Social Science & Medicine 96: 200-207 PMCID: PMC3804111 
• Emond J, Bernhardt A, Gilbert-Diamond D, Li Z and Sargent J (2016) Commercial TV exposure, fast-food 
toy collecting, and family visits to fast food restaurants among families living in rural communities. The 
Journal of Pediatrics 168:158-163 PMCID: PMC4698028 
              
 
 
 

Informed Consent Form 
Next generation ORS: ORS with calcium  
 
icddr,b protocol # PR-22091 
Version No. 1.0  
Version Date: October 19, 2022 
 
Protocol Title 
Next generation ORS: Randomized controlled trial comparing ORS with calcium vs standard ORS in reducing 
severity with acute watery diarrhea of adults. 
 
Investigators’ names 
Dr. Shafiqul A Sarker (Local PI) 
Dr. Dr. Sam Cheng (External PI)  
[List of other investigators is available on request] 
 
Funder 
The funder of this research is the National Institute of Health, USA.  
 
Organizations 
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh,  
University of Florida, Gainesville, USA 
University of Kentucky, Lexington, USA 
  
Conflicts of interest 
The Principal Investigators, Dr. Sam and Dr. Sarker, and the other research team members, have no conflicts of 
interest to declare.  
 
Since you have diarrhoea, and admitted in the Short Stay Unit or Longer Stay Unit, you are being asked to 
provide informed consent. Unless otherwise specified, the words “you” and “your” refer to you (i.e., the person 
participating in the research). The words “we” or “us” refer to study workers and investigators.  
 
Purpose of the research 
We invite you to take part in a clinical trial. Clinical trials are research studies that test if new ways to detect, 
prevent, or treat diseases work well, are safe, and whether they lead to any unexpected outcomes.  
 
Treatment of infectious diarrhea as remains a global challenge. Oral Saline and normal feeding are the most 
important parts of treatment of diarrhoeal diseases. These simple and inexpensive treatment saves millions of 
lives each year, but they do not shorten the duration of illness. Diarrhea causes losses of several ions from the 
body (one kind of salt like Na, K, Hco3 and minerals like Zn & Ca). The losses of salts are replaced through 
rehydration therapy and adding zinc but information on the role of Ca in diarrhea is limited.  Recently 
preliminary studies in humans show that, with replacement of Ca++, diarrhea was both promptly and dramatically 
reduced in both animals and humans at the University of Florida. However, so far, no formal randomized 
controlled trials (RCTs) on Ca++ replacement in diarrheal patients have been performed. At icddr,b (Cholera 
Hospital) we are carrying out a research study to examine if treatment with ORS and Ca reduce the severity 
and/or duration of diarrhoea in Bangladeshi population.  
Up to 396 participants will be asked to join this study. 
 
Invitation to participate 
You are being invited to join this study because: 
• 
Adult male  
• 
Non-pregnant adult female  
• 
Age between 18 and 60 years 
• 
History of acute watery diarrhea with signs of some OR severe dehydration  
• 
No bloody diarrhea 

• 
No signs of systemic infection that needed intravenous antibiotics 
 
Methods and procedures 
If you agree to our proposal of enrolling you, we will ask some questions about your health condition related 
to the current illness and before this illness; perform a thorough physical examination. Measure your weight, 
height, count pulse and respiratory rates, body temperature and record findings.  
 
A fresh stool specimen will be collected for detection of cholera. After initial rehydration and randomization, all 
cholera patients will receive antimicrobial therapy for cholera while all non-cholera patients will not. Participants 
will consume the assigned ORS (standard ORS or the investigational ORS) according to standard of care 
WHO/icddr,b guidelines, immediately after completion of rehydration and continued until cessation of diarrhea 
or 72 h after randomization, whichever comes first. Which of the products you will receive will depend on a 
process called “Randomization” (like flipping a coin) that will give you an equal chance to receive either of them. 
Neither any one of us nor you know which of the product you will have received. It will be disclosed only after 
analysis of the results. 
 
Two and half millilitre (half of a teaspoon) of venous blood will be collected only on enrolment for various 
laboratory tests that will allow us to assess disease condition and test results may help the doctors to treat you. A 
repeat sample will be drawn only when clinically indicated. A urine sample also will be collected for laboratory 
asses. 
 
If diarrhoea ceased, you will be discharged. Continuation of diarrhoea beyond 72 hours or consume more than 30 
L of the assigned ORS will constitute treatment failure and such cases you will be withdrawn from the study and 
will be treated according to the standard protocols of the hospital 
 
Risks and Potential benefits 
We do not expect any problem from ingesting the test product. You will be monitored closely for signs of any 
injury to health and referred for lab testing and medical care if necessary in the same manner as you would 
ordinarily obtain any other medical treatment.  At the time of collection of blood, you will feel a momentary pain 
due to needle prick. There also is a rare chance of bluish discolouration (bruish) surrounding the prick site, due to 
mild leaking of blood in the skin, which may result in a small bruise or swelling of the skin, and there is a very 
low chance of bleeding or infection. However, we will take required precaution including the use of disposable 
syringes and needles to prevent these problems and only well-trained personnel will collect this sample. In the 
event you may develop any of these problems, we will provide the best possible treatment at the Dhaka hospital 
of icddr,b at our own cost. 
 
You may benefit from the medical care that will be provided by the study up to next 7 days. The medical care 
provided to you during this period will be free of charge. If you require treatment for any injuries or illness 
related to your participation in the study, you should contact the investigators or icddr,b immediately. The 
information we learn may help your community and in similar places around the world by providing important 
information on whether the this ORS with Ca is effective to reduce diarrhoea severity and duration. 
 
Privacy, anonymity and confidentiality 
We will respect your privacy. No identifying information about you will be given to anyone or be published 
without your permission, unless the law requires us to do this. If you join this study, we will collect only the 
information we need for this study including some personal information that identifies you (name, address, 
phone number) for the purposes of contacting you. Data and samples related to the study will only be accessed 
by the research team or by people or institutions authorized by the Principal Investigators. Data Safety 
Monitoring Board (DSMB) that will particularly look at the reliability of data and safety of the test products, and 
the Ethical Review Committee (ERC) of icddr,b will have access to those information, which will be kept in a 
secured place under the supervision of the principal investigator of the study.    However, we would also like to 
inform you that disclosure of such information is subject to the laws of Bangladesh. At the time of publishing the 
results of this study, we will not use your name or identity. 
Signing this consent form does not give up your legal rights and does not change the legal and professional 
responsibilities of the study doctor(s) or involved institutions.  

 
Future use of information 
Your data collected during this study will be kept by the International Centre for Diarrhoeal Disease Research, 
Bangladesh (icddr,b), according to institutional policies for at least five years after the main study report is 
published. Data will only be used for scientific purposes to benefit society.  
 
Right not to participate and withdraw 
Participation is voluntary, meaning it is your choice to take part or not in this study. You can change your mind at 
any time. You will also be able to withdraw consent of participation at any time during the study without paying 
any penalty or effect on your/your family member treatment at the Dhaka hospital in future. If you decide to 
leave the study, you can contact the Principal Investigator or a member of the study team to let them know. The 
investigators will also have the right to withdraw you from the study if it is deemed to be in your best interest. 
 
Principle of compensation 
We will reimburse you up to a maximum of 400 BDT per visit for transportation costs between your home and 
icddr,b for wage loss.  
 
Communication 
If you have any question you can ask me right now or at any time later on. If you want to know anything about 
rights and benefits for participation in this study you can ask Mr M A Salam Khan, IRB Coordinator. The 
addresses are as follows: 
The addresses are as follows: 
 
Purpose of contact 
Name and address 
Address for communication 
For any question related to 
the study, or any problem 
Local PI :Shafiqul 
Alam Sarker 
Address: Nutrition and Clinical Services Division, 
icddr,b, 68 Shaheed Tajuddin Ahmed Sarani, 
Mohakhali, Dhaka 1212  
Mobile No.+8801713039813 
(to be open 7/24 hours) 
To know the rights or 
benefits or to log any 
complaint or dissatisfaction 
M A Salam Khan (IRB 
Coordinator) 
IRB Secretariat, Research Administration, icddr,b, 
Mohakhali, Dhaka-1212 
Phone: (+88-02) 9827084 or Mobile: 01711428989 
 
I am giving my consent to the investigator to join this study 
 
   Yes            
  No 
 
 
I am giving my consent to the investigator to obtain photos and videos 
  Yes            
  No 
 
I am giving my consent to give my provided information to other  
  Yes            
  No 
researchers on condition that my identifiable information  
cannot be disclosed or shared with anybody. 
 
I am giving consent to be contacted about additional  
 
 
  Yes            
  No 
research opportunities in the future. 
 
 
 
 
Participant’s name 
 
Participant’s signature or 
thumbprint 
Date (DD/MMM/YYYY) 

 
 
 
 
 
Name of witness to the 
consent discussion 
 
Signature of witness  
Date (DD/MMM/YYYY) 
 
 
 
 
 
Name of person who explained 
consent (representative of the 
PI) 
 
Signature of person who explained 
consent  
Date (DD/MMM/YYYY) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check-List 
 

Check-list for Submission of Research Protocol 
For Consideration of the Research Review Committee (RRC) 
[Please check all appropriate boxes] 
 
1. Has the proposal been reviewed, discussed and cleared by all listed investigators? 
 
  Yes                
  No 
If the response is No, please clarify the reasons:       
 
2. Has the proposal been peer-reviewed externally?  
 
  Yes               
  No                    
  External Review Exempted 
If the response is ‘No’ or “External Review Exempted”, please explain the reasons:       
 
 
If the response is “Yes”, please indicate if all of their comments have been addressed? 
  Yes (please attach)              
 
  No (please indicate reason(s)): 
 
3. Has the budget been reviewed and approved by icddr,b’s Finance Office? 
  Yes                
 No (reason): ________________________________________________________________ 
4. Has the Valid Ethics Certificate(s) been attached with the Protocol? 
 
  Yes                
  No  
If the answer is ‘No’, please explain the reasons:       
5. Has the Bangla & English Information Sheets and Consent Forms been attached with the protocol? 
 
 Yes            
 No            
 Not applicable 
6. Has the Bangla & English Tools/Questionnaire been attached with the protocol? 
 
       
 Yes            
 No            
 Not applicable 
7. Has the list of abbreviations been attached with the Protocol? 
 
  Yes                
  No  
If the answer is ‘No’, please explain the reasons:       
 
 
 
 
 
_______________________________                                                                                                        _________            
Signature of the Principal Investigator 
                                                                                                    Date             
                                                               
 
 
 
 
 
 
 
 
 
College of Medicine 
1600 SW Archer Rd 
Department of Pediatrics 
PO Box 100296 

 
Gainesville, FL 32610-0296 
 
(352) 392-3337 
 
(352) 392-0481 fax 
 
 
September 21, 2022 
 
 
 
 
 
 
 
 
Dr. Md. Shafiqul Alam Sarker 
ICDDR, B 
Bangladesh  
 
 
RE: Next Generation ORS: Randomized controlled trial comparing ORS with calcium vs  
standard ORS in reducing severity of adults with acute watery diarrhea 
 
Impact score: 20 
 
 
Dear Dr. Sarker, 
 
 
I am so excited for the favorite result by the reviewers on the aforementioned 
NIH grant clinical trial and anticipate to work with you on this project if funded 
 
Sincerely, 
 
 
 
Sam X Cheng, MD, MSc, PhD 
Associate Professor 
Pediatrics, Gastroenterology, Hepatology, and Nutrition 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
College of Medicine 
1600 SW Archer Rd 

Department of Pediatrics 
PO Box 100296 
 
Gainesville, FL 32610-0296 
 
(352) 392-3337 
 
(352) 392-0481 fax 
 
 
September 21, 2022 
 
 
 
 
 
 
 
 
Dr. Md. Shafiqul Alam Sarker 
ICDDR, B 
Bangladesh  
 
 
RE: Next Generation ORS: Randomized controlled trial comparing ORS with calcium vs  
standard ORS in reducing severity of adults with acute watery diarrhea 
 
Impact score: 20 
 
 
Dear Dr. Sarker, 
 
 
I am so excited for the favorite result by the reviewers on the aforementioned 
NIH grant clinical trial and anticipate to work with you on this project if funded 
 
Sincerely, 
 
 
 
Sam X Cheng, MD, MSc, PhD 
Associate Professor 
Pediatrics, Gastroenterology, Hepatology, and Nutrition