Clinical trial NCT03941288
Conditions: Gastroparesis Dyspepsia
Sponsor: Mayo Clinic
Start date: 2019-09-04; Completion date: 2023-02-23
Enrollment: 92 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Researchers are looking at the effects of a cannabidiol medication on stomach function in people with gastroparesis (a paralyzed stomach) and people with dyspepsia (an upset stomach caused by improper functioning of the stomach's muscles or nerves).

Detailed description:

Arms: arm 1: Cannabidiol will be administered orally twice daily in equally divided doses starting at 2.5mg/kg per day and increasing by 2.5 to 5.0mg/kg every other day until the target dose of 20mg/kg is reached.

Cannabidiol and the matching placebo solution (excipients alone) will be provided in identical 100ml amber glass bottles. At the end of the treatment period, the treatment solutions will be tapered (10% volume each day) over 10 days. arm 2: Placebo will be administered orally twice daily in equally divided doses starting at 2.5mg/kg per day and increasing by 2.5 to 5.0mg/kg every other day until the target dose of 20mg/kg is reached.

Cannabidiol and the matching placebo solution (excipients alone) will be provided in identical 100ml amber glass bottles. At the end of the treatment period, the treatment solutions will be tapered (10% volume each day) over 10 days.
Interventions: intervention 1: Cannabidiol intervention 2: placebo
Intervention descriptions: intervention 1: Cannabidiol and the matching placebo solution (excipients alone) will be provided in identical 100ml amber glass bottles. At the end of the treatment period, the treatment solutions will be tapered (10% volume each day) over 10 days.

In accordance with Food and Drug Administration guidance, prior to starting treatment and at end of 1 month treatment, we shall obtain serum transaminases (alanine and aspartate) and total bilirubin levels. These tests will also be performed if patient develops clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, right upper quadrant abdominal pain, fatigue, anorexia, or jaundice and/or dark urine); if such features develop the treatment will be interrupted or discontinued. intervention 2: Cannabidiol and the matching placebo solution (excipients alone) will be provided in identical 100ml amber glass bottles. At the end of the treatment period, the treatment solutions will be tapered (10% volume each day) over 10 days.

In accordance with Food and Drug Administration guidance, prior to starting treatment and at end of 1 month treatment, we shall obtain serum transaminases (alanine and aspartate) and total bilirubin levels. These tests will also be performed if patient develops clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, right upper quadrant abdominal pain, fatigue, anorexia, or jaundice and/or dark urine); if such features develop the treatment will be interrupted or discontinued.

Protocol documents:
Prot_SAP_001.pdf: 
 
Pharmacodynamics, 
Pharmacogenetics, Clinical 
Efficacy and Safety of 
Cannabidiol for Gastroparesis 
and Functional Dyspepsia 
 
NCT# 03941288 
 
September 14, 2022 


Version 12 dated  9/14/2022 
 
PROTOCOL TITLE: 
Pharmacodynamics, Pharmacogenetics, Clinical Efficacy and Safety of Cannabidiol for Gastroparesis 
and Functional Dyspepsia 
Principal Investigator:  Michael Camilleri, MD 
Co-Investigators: Daniel Maselli, MD; David Katzka, MD; Duane Burton, MHA;  
Statisticians: W. Scott Harmsen, MS; Mariza de Andrade, PhD 
Study Coordinators:  Deb Eckert RN, Margaret Breen-Lyles, Ann Taylor, Monique Torres 
 
ABSTRACT  
Gastroparesis is defined as a gastrointestinal motility disorder with objectively delayed gastric emptying in the 
absence of mechanical obstruction. Gastroparesis is associated with upper gastrointestinal symptoms 
including early satiety, postprandial fullness, nausea, vomiting, bloating, and upper abdominal pain. The 
diagnosis of gastroparesis is based on the combination of symptoms of gastroparesis, absence of gastric outlet 
obstruction or ulceration, and delay in gastric emptying (4 hour gastric emptying test). Similar symptoms may 
also accompany other mechanisms of gastric dysfunction including reduced gastric accommodation and 
gastric hypersensitivity. Together, these gastric motor and sensory abnormalities may cause functional 
dyspepsia. Functional dyspepsia is a very common cause of substantial morbidity; it is estimated to affect 10% 
of the population and manifests as abdominal pain/discomfort after eating for at least three days per week. It 
has been estimated that 40% of patients with this symptom complex consult their physicians, with impact on 
their workplace attendance and productivity and an economic impact in excess of $18 billion in 2009.  
Development of effective treatments of these disorders is desirable, given significant unmet medical need. The 
only approved drug for gastroparesis is metoclopramide, a dopamine D2 antagonist and 5-HT4 agonist; it can 
be prescribed for a minority of patients for up to 3 months because of endocrine, cardiac and neurological side 
effects. There is no currently approved treatment for functional dyspepsia. The non-selective cannabinoid 
receptor agonist, dronabinol, was previously shown to retard gastric emptying and enhance gastric 
accommodation. Δ9THC and non-pharmaceutical grade cannabidiol are used for diverse pain-related disorders; 
the effects and benefit-risk ratio of these agents are unclear. With recent FDA approval of cannabidiol, our 
general hypothesis is that cannabidiol relieves symptoms in patients with gastroparesis and functional 
dyspepsia without deleterious effects on gastric emptying, accommodation, satiation or satiety. Our aims are:  
1. To compare the pharmacodynamics and clinical effects of cannabidiol vs. placebo on satiation, fasting 
gastric volume, gastric accommodation, gastric emptying, and symptoms in patients with: 
1A. gastroparesis (symptoms based on Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD); and 
1B. functional dyspepsia (+ non-delayed gastric emptying) and symptoms based on Nepean Dyspepsia Index        
2. To assess pharmacogenetics effects of variants in FAAH and CNR1 genes on the pharmacodynamics 
effects of cannabidiol compared to placebo on fasting and accommodation gastric volumes, gastric emptying 
and satiation. 
Anticipated Results and Significance: We expect these studies will lead to understanding the mechanisms 
of action of cannabidiol in improving gastrointestinal functions and patient reported outcomes, including pain, in 
patients with gastroparesis or functional dyspepsia, addressing unmet needs of millions of American citizens.  
 
 
 
 


Specific Aims  
    Gastroparesis is defined as a gastrointestinal motility disorder with objectively delayed gastric emptying in 
the absence of mechanical obstruction that is associated with upper gastrointestinal symptoms including early 
satiety, postprandial fullness, nausea, vomiting, bloating, and upper abdominal pain. The most common 
etiologies of gastroparesis are diabetes mellitus, post-surgical, and idiopathic; less common are iatrogenic, 
extrinsic neuronal (such as Parkinsonism and paraneoplastic disease), and infiltrative disorders (such as 
scleroderma). The diagnosis of gastroparesis is based on the combination of symptoms of gastroparesis, 
absence of gastric outlet obstruction or ulceration, and delay in gastric emptying (4 hour gastric emptying test). 
The initial management of gastroparesis is based on dietary therapy for restoration of fluids and electrolytes, 
nutritional support, and treating the underlying etiology such as optimization of glycemic control in diabetics. 
The dietary therapy should be supported with prokinetic agents to accelerate gastric emptying and improve 
gastroparesis symptoms. Development of effective pharmacologic therapies for such disorders is desirable, as 
these conditions represent a significant unmet medical need; the only approved drug is metoclopramide, a 
dopamine D2 antagonist and 5-HT4 agonist, which is approved for a minority of patients for a period of only 
three months because of endocrine, cardiac and neurological adverse effects. Given the paucity of available 
efficacious treatments, devices (such as stents), per-oral endoscopic myotomy of the pylorus, and electric 
stimulation or surgery are being performed without proven benefit in sham controlled trials. 
    Functional dyspepsia is estimated to affect ~10% of the population and manifests as abdominal pain after 
eating for at least three days per week. It causes substantial morbidity, impacts workplace attendance and 
productivity, and had an economic impact in excess of 18 billion dollars in 2009. There is no currently approved 
treatment for functional dyspepsia. Current medical treatment includes eradication of H pylori, acid 
suppression, prokinetic drugs, antidepressants, and psychological and alternative therapy; yet, despite this, 
many patients remain refractory to treatment, experiencing continued disabling symptoms including 
postprandial pain. Although subgroups of functional dyspepsia patients also have delayed or accelerated 
gastric emptying, other mechanisms include reduced gastric accommodation and gastric hypersensitivity.  
Given the extensive use of Δ9THC and cannabidiol for diverse pain-related conditions, the effects and benefit-
risk ratio of these agents is unclear. With recent FDA approval of pharmaceutical grade cannabidiol, there is 
potential to provide patients with relief.  
    In our prior studies [NIH R01-DK079866 (09-11)], the non-selective cannabinoid receptor agonist dronabinol 
(DRO) was previously shown to retard gastric emptying especially in female patients, increase fasting gastric 
volume in males, and inhibit colonic tone and phasic pressure activity. However, DRO did not significantly alter 
thresholds for first, gas or pain sensation during stepwise distension in the descending colon; paradoxically, 
DRO increased sensory rating for pain during random-order phasic distensions. The endo-cannabinoid system 
consists of CB1 and CB2 receptors; the ligands of these receptors are anandamide and 2-arachidonyl glycerol 
(2-AG), and their respective ligand-inactivating enzymes are fatty acid amide hydrolase (FAAH) and 
monoacylglycerol lipase (MGLL). It is conceivable that variants in pivotal genes involved in the inactivation of 
the endocannabinoids or the CBR1 receptor could impact the response to administered cannabinoid agonist. 
Indeed, we previously showed two significant treatment-by-genotype interactions: DRO preferentially delays 
colonic transit in those with the CNR1 rs806378 (CT/TT vs. CC) genotypes; DRO influences fasting colonic 
motility index in IBS (with diarrhea or alternating bowel function) who carry FAAH rs324420 (CA/AA vs. CC).  
    Our general hypothesis is that cannabidiol relieves symptoms in patients with gastroparesis and functional 
dyspepsia without deleterious effects on gastric emptying, satiation or satiety. We shall assess effects on 
symptoms using validated patient reported outcomes.  
Overall Aim 1: To compare the pharmacodynamics and clinical effects of cannabidiol vs. placebo on satiation, 
fasting gastric volume, gastric accommodation, gastric emptying, and symptoms in patients with:  
Aim 1 a. gastroparesis with symptoms based on American Neurogastroenterology Motility Society’s 
Gastroparesis Cardinal Symptom Index (GCSI)-Daily Diary; or Aim 1 b. functional dyspepsia (with normal 
gastric emptying of solids) with symptoms based on Nepean Dyspepsia Index.        
Aim 2. To assess pharmacogenetics effects of variants in FAAH and CNR1 genes on the pharmacodynamics 
effects of cannabidiol vs. placebo on fasting and accommodation gastric volumes, gastric emptying and 
satiation in the same patients.  
Anticipated Results and Significance: We expect these studies will lead to understanding the mechanisms 
of action of cannabidiol in improving gastrointestinal functions and patient reported outcomes including pain in 
the same patients with gastroparesis or functional dyspepsia; thus, our studies will address unmet needs of 
millions of American citizens.  


Background on Gastroparesis and the Related Disorder, Functional Dyspepsia  
 
Gastroparesis is defined as a gastrointestinal motility disorder with objectively delayed gastric emptying 
in the absence of mechanical obstruction that is associated with upper gastrointestinal symptoms including 
early satiety, postprandial fullness, nausea, vomiting, bloating, and upper abdominal pain (1,2). The most 
common etiologies of gastroparesis are diabetes mellitus, post-surgical, and idiopathic; less common are 
iatrogenic, extrinsic neuronal (such as Parkinson’s disease and paraneoplastic disease), and infiltrative 
disorders (such as scleroderma) (3,4). The diagnosis of gastroparesis is based on the combination of 
symptoms of gastroparesis, absence of gastric outlet obstruction or ulceration, and delay in gastric emptying [4 
hour gastric emptying test (2)]. The management of gastroparesis is based on dietary therapy for restoration of 
fluids and electrolytes, nutritional support, and treating the underlying etiology such as optimization of glycemic 
control in patients with diabetes. Dietary therapy should be supported with prokinetic agents to accelerate 
gastric emptying and improve gastroparesis symptoms. Devices such as stents, and endoscopic approaches 
such as per-oral endoscopic myotomy of the pylorus, electric stimulation, or surgery are being proposed (5). 
 
Functional dyspepsia (FD) is a very common cause of substantial morbidity, estimated to affect 10% of 
the population, and manifest as abdominal pain/discomfort after eating that is present at least three days per 
week. It has been estimated that 40% of patients with this symptom complex consult their physicians, with 
impact on their workplace attendance and productivity and an economic impact in excess of 18 billion dollars in 
2009 (6). The pathophysiology of FD is most likely heterogeneous, with different underlying mechanisms 
contributing to somewhat more specific diverse symptom patterns (7). Impaired gastric accommodation to a 
meal and delayed gastric emptying and hypersensitivity to gastric distention are the mechanisms classically 
implicated in postprandial distress syndrome (a subtype of FD that is typically associated with normal gastric 
emptying). Impaired gastric accommodation to a meal is present in up to 50% of patients with FD, is 
associated with early satiation and weight loss, and may result in redistribution of the meal to the distal 
stomach and more rapid gastric emptying (8). Visceral hypersensitivity is present in approximately one-third of 
patients with FD and is associated with higher intensity ratings of all epigastric symptoms including pain (9). 
Visceral hypersensitivity is supported by functional brain imaging studies or lack of anti-nociceptive response to 
gastric signals and by co-morbid psychosocial disorders such as anxiety, depression and somatization. 
Delayed gastric emptying occurs in up to one-third of patients with FD and, in some series, has been 
associated with postprandial fullness, nausea and vomiting. More recently, impaired duodenal mucosal 
integrity, with low-grade mucosal inflammation characterized by eosinophils and mast cells, has been reported 
as a putative pathophysiological mechanism in FD (10,11).  
Current medical treatments include eradication of H. pylori, acid suppression, prokinetics, 
antidepressants, and psychological and alternative therapies; yet, despite this, many patients remain refractory 
to treatment, experiencing continued disabling symptoms (12).  
Development of effective pharmacologic therapies for such disorders is desirable, as these conditions 
represent a significant unmet medical need. In clinical practice, more and more patients are resorting to the 
use of cannabis or opioids, or registering for medical marijuana or opioid treatment through their state-
approved process for relief of abdominal symptoms. The symptoms include nausea, dyspepsia and abdominal 
pain based on functional gastrointestinal (GI) disorders (FGID) (13), as well as relief of symptoms 
unresponsive to biologics in patients with inflammatory bowel disease, in whom there are increasing trends of 
opioid use disorder (14), especially in those with sustained poor quality of life (15).   
 
Potential of Cannabinoid Agents in Treatment of Non-malignant Gastrointestinal Diseases 
    The endocannabinoid system consists of CB1 and CB2 receptors; the ligands of these receptors are 
anandamide and 2-arachidonyl glycerol (2-AG), and their respective ligand-inactivating enzymes (16) are fatty 
acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGLL). Endocannabinoids are synthesized in 
post-synaptic neurons and act as retrograde messengers binding to the presynaptic CB1 receptor through 
various effectors, reducing activity of protein kinases, modulating ion channels and neurotransmitter release, 
e.g., acetylcholine.  Endocannabinoids may also activate the transient receptor potential (TRP) vanilloid type 1 
(TRPV1), which is mainly expressed by primary afferent neurons and the orphan G protein-coupled receptors 
such as GPR555. Exogenous or administered cannabinoids can activate the same presynaptic receptors to 
modulate neurotransmitter release or sensory receptors.   


Cannabinoids are involved in the 
regulation of food intake, nausea and 
emesis, gastric secretion and gastro-
protection, gut motility, ion transport, 
visceral sensation, intestinal 
inflammation and cell proliferation in 
the gut (17). In prior studies, we 
assessed the potential role of genetic 
variations in cannabinoid genes for 
their associations with GI phenotypes 
as indirect evidence of the role of 
cannabinoid mechanisms in GI 
diseases and functions. The 
associations with phenotypes such 
as the symptoms based on Rome 
III/IV criteria for FGID, including 
bowel dysfunction and pain, colonic 
transit, colonic sensation, gastric 
volume and satiation, support the 
notion that the endocannabinoid 
system modulates gastric and 
colonic functions.  These are 
documented by our published 
observations based on in 62 
overweight/obese subjects for gastric phenotype, 75 irritable bowel syndrome (IBS) patients (35 IBS-D, 35 IBS-
C, 5 IBS-A) for colonic sensation and motility index measurements, 102 IBS patients for rectal sensation 
(18,19). We also previously reported association of genetic variants in FAAH and CNR1 and IBS symptoms, 
motor and sensory phenotypes based on 455 FGID patients and 228 healthy controls (18-20).  
a. FAAH (C385A; rs324420) CA/AA genotype increases the odds (relative to HV) for IBS-D (P=0.008), 
IBS-alternating (IBS-A) (P=0.012) and chronic abdominal pain (P=0.055). 
b. FAAH rs324420 CA/AA genotype was associated with accelerated colonic transit in IBS-D (P=0.037). 
c. CNR1 rs806378 (P=0.014; CC vs. CT/TT) was associated with colonic transit in IBS-D; the TT group 
had the fastest colonic transit at 24 and 48 hours.  
d. CNR1 rs806378 was associated with colonic higher sensation rating (CT/TT vs. CC) of gas (P=0.025) 
in the IBS-D or IBS-A groups. 
e. FAAH rs324420 (CA/AA vs.CC) influences fasting colon motility index in patients with IBS-D and IBS-A. 
f. CNR1 rs806378 genotype associated with reduced fasting gastric volume (CC vs. CT/TT) (P=0.031). 
Figure 1. Synthesis, action, hydrolysis of endocannabinoids (from 
Camilleri 2018 (16) 


g. FAAH rs324420 CC genotype was associated with a lower maximum tolerated volume (MTV) 
of Ensure® in a lab-based satiation test compared to 
CA/AA group (P=0.046). 
These observations also provide further rationale for 
proposing pharmacological modulation of the 
cannabinoid mechanisms to normalize gastric 
functions in patients with functional gastrointestinal 
disorders.  
We choose to focus on the upper gastrointestinal 
diseases because of the greater unmet clinical need. 
While there are several potential selective agonists 
and antagonists used in experimental animal studies 
(Table 1), to date the only one available for human 
studies has been dronabinol (DRO), a non-selective 
cannabinoid receptor agonist.  
Pharmacology and Actions of Cannabidiol  
A novel phytocannabinoid agent has been recently 
approved [Epidiolex® (cannabidiol)] by the FDA for 
use in seizure disorders. A selective CB2 receptor 
agonist (APD371) is being studied in IBD and pain 
(Clinical Trials .gov Identifier: NCT03155945) but is 
not available for research. The rationale for focusing 
on CB2 receptor agonist is provided below.  From a 
recent review in Nature Reviews in Drug Discovery (21), several synthetic CB1 or CB2 modulators are being 
tested for diverse indications (GW842166, S-777469, JBT-101 [all CB2 selective agonists], SAB378, NEO1940 
[both peripherally-restricted CB1 and CB2 receptor agonists], and PF‑04457845, URB597, V158866, JNJ‑
42165279, BIA 10‑2474 [FAAH inhibitors] and PF‑06818883 and ABX‑1431 [both MAGL inhibitors]), but they 
are not available for our studies.  
We propose to focus our studies on cannabidiol (CBD) 
because of its approval status by FDA, its new availability as 
a pharmaceutical grade preparation, and increased evidence 
of its potential in the relief of pain and discomfort cannabidiol 
while being generally regarded as being devoid of “euphoric” 
cannabinoid-like side effects in contrast to Δ9THC; 2-D 
structures of the 2 compounds are shown in Figure 2. 
The potential modes of benefit of cannabidiol include: 
a. 
targeting (as an inverse agonist) of G protein-coupled receptors 3, 6, and 12 [GPR3, GPR6 (22), and 
GPR12 (23)], a family of closely-related orphan receptors that are phylogenetically most closely related to the 
cannabinoid receptors, and are reported to play important roles in many normal physiological functions and to 
be involved in a variety of pathological conditions. For example, GPR3 (24) orphan receptor is involved in 
neuropathic pain after peripheral nerve injury and regulates morphine-induced anti-nociception. 
     Δ9THC                       cannabidiol 
Figure 2.  2-dimensional molecular structures 
of Δ9THC and cannabidiol 
Table 1. Potential selective agonists and antagonists 
used in experimental animal studies 


b. non-psychotropic plant cannabinoids, 
including cannabidiol, dose-dependently 
activate and rapidly 
desensitize TRPV1, as well as TRP channels of 
subfamily V type 2 (TRPV2) and subfamily A 
type 1 (TRPA1), based on patch clamp analysis 
in transfected HEK293 cells (25).  
c. anti-inflammatory effects, which are thought 
to be mediated by effects of cannabidiol on 
CB2 receptors (26), impacting diverse cellular 
functions, as  summarized in Figure 3, that may 
lead to neuroprotection. Cannabidiol appears to 
stimulate synaptic plasticity and facilitates 
neurogenesis that may explain its positive 
effects on attenuating psychotic, anxiety, and 
depressive behaviors. 
d. targeting 5-HT1A receptors (25) for relief of 
experimental pain; note that 5-HT1A receptors 
modulate gastric accommodation (27). 
Conversely, the literature suggests the effects of other cannabinoid agents on pain are controversial: 
A.  A Cochrane review (28) concluded that potential benefits of cannabis-based medicine (herbal cannabis, 
plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed 
by their potential harms. 
B.  A separate systematic review that included 24 RCTs and 1334 patients concluded that, though some RCTs 
showed a clinically significant improvement with a decrease of pain scores, the majority of the studies did not 
show an effect on pain (29), possibly indicating an effect on well-being or mood, rather than pain sensation. 
C.  An experimental brain imaging study showed that different cannabinoid-based drugs had heterogeneous 
effects on brain imaging (30), anxiety and the perception of experimentally-induced pain. 
D.  Thus, Δ9THC increased anxiety, and levels of intoxication, sedation, and psychotic symptoms, whereas 
there was a trend for a reduction in anxiety following administration of cannabidiol in addition to a reduction in 
only the affective, but not the sensory perception of pain, which was associated with reduced blood 
oxygenation level-dependent signal in “affective regions” such as amygdala and the anterior and posterior 
cingulate cortex rather than the frontal and somatic cortex.  
E.  A randomized, controlled trial of Δ9THC and placebo in 3 forms of chronic abdominal pain showed no 
significant effects of treatment with Δ9THC (31). 
Published Human Data on Pharmacodynamics and Pharmacogenetics with Cannabinoid Agonist 
In our prior studies (16,32,33) [NIH R01-DK079866 Cannabinoid mechanisms in human GI motor & sensory 
functions], we have shown that DRO retarded gastric emptying especially in female patients (Figure 4) and 
increased fasting gastric volume in males, and inhibited colonic tone and phasic pressure activity (Figure 5). 
 
 
 
 
 
 
 
 
 
 
 
 
However, DRO did not significantly alter thresholds for first gas or pain sensation during stepwise distension in 
the descending colon, but increased sensory rating for pain during phasic distensions. DRO may worsen pain. 
Figure 3. Cellular targets of cannabidiol (and 
endocannabinoids) include neurons, endothelial cells, 
oligodendrocytes and microglial cells (from reference 26) 
Figure 4. DRO retards gastric 
emptying especially in females 
Figure 5. Colonic tone and phasic pressure activity measured with 
intracolonic DRO inhibits postprandial phasic contractility and tone 
(reduced volume under barostat conditions 


It is conceivable that biological variations in inactivation of the endocannabinoids or in the CBR1 
receptor could impact the response to exogenously administered cannabinoids. Our prior studies also 
assessed the potential role of genetic variations in cannabinoid genes for their associations with 
pharmacological responses to DRO (pharmacogenomics) (34). Thus, we demonstrated, in patients with IBS-D, 
a treatment-by-genotype effect whereby DRO preferentially delayed colonic transit in those with the CNR1 
rs806378 CT/TT genotypes. There was no significant interaction of treatment with FAAH rs324420 detected. 
 
Gaps in Current Knowledge and Unmet Clinical Needs 
 
There have been no new medications approved for patients with gastroparesis and functional 
dyspepsia since 1979. The only currently approved medication, metoclopramide, is poorly efficacious, is 
associated with an FDA black box warning, and often results in adverse neurological effects, some of which, 
like tardive dyskinesia, can be permanent. There is a need for new medications. While there are multiple 
potential positive effects of cannabidiol on pain mechanisms, it is still unclear whether they benefit visceral 
pain and other symptoms in humans. However, the potential combination of effects on pain mechanisms, as 
well as neuroprotective anti-inflammatory effects suggest cannabidiol differs significantly in its potential efficacy 
and safety (without inducing anxiety or euphoric effects) relative to Δ9THC.    
Our lab is uniquely poised to conduct the proof of concept and clinical studies necessary to 
start new approaches to treat patients with these conditions which are associated with high morbidity. 
 
APPROACH: GENERAL METHODS 
Study Design, Randomization and Allocation  
We shall conduct randomized, double blind, placebo-controlled, parallel-group trials of the effects 
of cannabidiol on gastric motor functions, satiation, and symptoms during 4 weeks’ treatment in single-center 
studies in patients with gastroparesis (aim 1A) or functional dyspepsia with non-delayed gastric emptying of 
solids (aim 1B). In addition to 4 weeks of treatment there is another week required for de-escalating the study 
medication, so the patients will be on treatment for a total of 5 weeks. A randomization schedule, computer-
generated by the study statistician’s office, will be submitted to the Mayo Clinic CCaTS Research Pharmacy. 
Allocations will be concealed; studies will be blinded until locked data are transmitted to the statistician.  
Participants Eligibility Criteria 
 
Patients with gastroparesis or functional dyspepsia (Appendix 1), age 18-70 years, will be recruited and 
enrolled after providing written informed consent. Patients will be identified from among Mayo Clinic patients or 
non-Mayo patients through Clinicaltrials.gov .Patients will have symptoms consistent with gastroparesis based 
on a national guideline (2) for gastroparesis (symptoms PLUS delayed gastric emptying of solids).     Patients 
with  Rome IV criteria for postprandial distress syndrome (a subset of functional dyspepsia) (35) will be 
selected based on gastric emptying of solids which is NOT delayed, in addition to standard FD criteria: 
1. Symptoms fulfilled for the last 3 months with onset >6 months before diagnosis:   
2. > One symptom being bothersome: postprandial fullness, early satiation, epigastric pain or burning 
3. Must include one or both of the following at least 3 days per week: 
    a.  Bothersome postprandial fullness (i.e., severe enough to impact on usual activities) 
    b.  Bothersome early satiation (i.e., severe enough to prevent finishing a regular-size meal) 
4. No evidence of organic, systemic, or metabolic disease to explain the symptoms on routine investigations.    
Participants will have previously undergone test of gastric emptying of solids using the standardized Mayo 
Clinic scintigraphic method (4h 320kcal egg, 30% fat meal). Subjects may be involved in study activity for up to 
10 weeks from screening to completion.  In the event that a potential participant with reasonable clinical 
evidence of gastroparesis has not previously undergone testing of gastric emptying of solids using the 
standardized Mayo Clinic scintigraphic method, gastric emptying testing done at baseline may be used to 
determine eligibility.  


     In recent studies from our clinical motility group 
(37,38), we identified 1276 patients with upper 
gastrointestinal symptoms who were evaluated at 
Mayo Clinic over a 15-year period, and whose 
records were accessed through the electronic 
medical record:  953 females (74.0%); mean age was 
43.1±15.4 years (SD), and the mean BMI was 
24.7±6.2 kg/m2. There were 175 (13.6%) who had 
treated hypothyroidism, 109 (8.54%) with diabetes, 
and 20.8% with psychological or psychiatric 
disorders. These data (37) suggest that results from 
studies on patients included in our study will provide 
generalizable data. 
     Standard inclusion criteria will include: ability to provide informed consent, absence of other diseases 
(structural or metabolic) which could interfere with interpretation of the study results, body mass index of 18-40 
kg/m2 and, for females, must not be pregnant or lactating due to administration of study medications and 
radiation exposure, stable doses of thyroid replacement, estrogen replacement, low-dose aspirin for 
cardioprotection, and birth control (but with adequate backup contraception, as drug interactions with birth 
control have not been conducted for secretin PAM) are permissible. Also subject will be included if they are on 
stable (no change in past month) doses of the following medications listed in table 1b.  
 
 
Specific eligibility criteria regarding gastric emptying (320kcal, 30% fat meal) in different specific aims will be: 
a. For gastroparesis (aims 1a ): <25% emptied at 2 hours for females and <28.4% emptied at 2 hours 
for males, and/or >23.8% retained for females (<76.2 emptied) at 4 hours and >23% retained for 
males (<77% emptied) at 4 hours
 
b. For functional dyspepsia (aim 1b): <25% retained at 4 hours (i.e., normal gastric emptying of solids) 
Participants will have baseline screen for anxiety and depression by questionnaire (Appendix 2). 
Exclusion Criteria: 
1. Patients with current H. pylori infection will be excluded. 
2. Pregnancy or lactation 
3. Ultra-rapid metabolizers for CYP2C19 [estimated prevalence of 17% and 18% respectively based on 
literature review (36)] will be excluded since this could impact assessment of effects of cannabidiol 
4. Patients with abnormal baseline liver transaminases (greater than two times the upper limit of normal), 
since up to 3-fold, dose-related elevations of liver transaminases (ALT and/or AST) occur in 13% of treated 
patients (vs. 1% placebo); 
5. Hypersensitivity to cannabidiol or any of the ingredients in EPIDIOLEX 
6. Concomitant use of valproate, other hepatotoxic drugs 
Figure 6. Pie chart showing percentages of gastric 
motor functions in 1276 patients (37) with functional 
upper GI symptoms and 108 patients with diabetes 


7. The subject has HbA1c > 12% 
8. The subject is unable to withdraw any of the following medications listed in table 1a 48 hours prior to 
the study 
9. The subject has participated in another interventional clinical study within the past two weeks.  
10. History of recent surgery (within 60 days of screening) 
11. The subject has a history diagnosis of post-surgical gastroparesis 
12. A subject who in the determination of the investigator, possesses any condition that the investigator 
believes would put the subject at risk or would preclude the subject from successfully completing all 
aspects of the study.  
13. Concomitant use of CNS depressants and/or alcohol within 48 hours of GI testing, unless able to 
maintain a consistent dosage throughout the study  
 
Table 1a. Excluded Medications 
• 
Drugs known to affect gastrointestinal transit or motor functions 
• 
GLP-1 receptor or amylin agonists in patients with diabetes mellitus.  
• 
Drugs known to alter NI transit including laxatives, magnesium or aluminum-containing antacids, 
prokinetics, erythromycin.  Laxatives may be allowed per physician discretion if participants are still 
experiencing symptoms and if able to maintain a stable dose throughout the study. 
• 
Opiates, including: dextropropoxyphene, tramadol, ketobemidone, methadone 
• 
Antidiabetic treatment with pramlintide or glucagonlike peptide-1 receptor agonists. 
• 
Phencyclidine 
• 
Participants using Zofran for symptom management may be included per physician discretion if the 
dosage is stable and remains consistent throughout study participation. 
 
Table 1b. Included Medications: 
• 
Amitriptyline up to 50mg per 24 hours 
• 
Nortriptyline up to 50mg per 24 hours 
• 
Venlafaxine up to 150mg per 24 hours 
• 
Duloxetine up to 120mg per 24 hours 
• 
Paroxetine up to 50mg per 24 hours 
• 
Escitalopram up to 20 mg per 24 hours 
• 
Bupropion up to 300mg per 24 hours 
• 
Buspirone up to 30mg per 24 hours 
• 
Quetiapine up to 50mg per 24 hours 
• 
Citalopram up to 40 mg per 24 hours 
• 
Fluoxetine up to 60 mg per 24 hours 
• 
Sertraline up to 100 mg per 24 hours 
• 
Fluvoxamine up to 100 mg daily 
• 
Gabapentin up to 1200mg daily  
• 
Pregabalin up to 150mg daily 
 
Baseline safety blood tests in all patients: 
a. Serum creatinine, bilirubin, ALT, AST 
b. CYP3A4 or CYP2C19 (pharmacogenetics)   
c. Urine pregnancy test 
Medication, Doses, and Mode of Administration  
Cannabidiol or placebo will be administered as in trials for childhood syndromic seizure disorders (39-
41), orally twice daily in equally divided doses starting at 2.5mg/kg per day and increasing by 2.5 to 5.0mg/kg 
weekly until the target dose of 20mg/kg is reached. The active treatment is a plant-derived pharmaceutical 
formulation of purified cannabidiol oral solution (100mg per milliliter). Cannabidiol and the matching placebo 


solution (excipients alone) will be provided in identical 100ml amber glass bottles. At the end of the treatment 
period, the treatment solutions will be tapered (10% volume each day) over 7 days.  
In accordance with FDA guidance, prior to starting treatment and at end of 1 month treatment, we shall obtain 
serum transaminases (ALT and AST) and total bilirubin levels. These tests will also be performed if patient 
develops clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, 
right upper quadrant abdominal pain, fatigue, anorexia, or jaundice and/or dark urine); if such features develop 
the treatment will be interrupted or discontinued. 
Common adverse events (>10% frequency) in the cannabidiol trials for childhood seizure disorders were 
somnolence, vomiting, fatigue, pyrexia, upper respiratory tract infection, decreased appetite, convulsion, 
lethargy, somnolence, and diarrhea. Elevated aminotransferase levels have been observed. In the trials to 
date, cannabidiol lacked the psycho-activity of the archetypal cannabinoid, Δ9THC, consistent with lack of 
appreciable affinity or activity at the cannabinoid receptors. Cannabidiol did not provoke suicidality. As a 
precaution, we shall use the approved assessment instrument, the Columbia Suicide Severity Rating Scale 
(Appendix 3) and the study team will assess the patients by phone at weeks 1 and 2, and in person at week 4. 
If suicidal thoughts and behavior emerge during treatment, the treatment will be discontinued. 
Randomization:  A randomization schedule, computer-generated by the study statistician’s office, will be 
submitted to the Mayo Clinic CCaTS Research Pharmacy. Allocations will be concealed. Medications will be 
stored in a monitored, climate-controlled environment according to manufacturer’s directions. Monitoring 
records will be available for review to ensure quality control.  
Quantitative Traits: On different days, participants 
will attend Mayo Clinic Clinical Research Trials Unit 
(CRTU) after an 8-hour fasting period, and validated 
quantitative traits will be measured. 
Gastric Accommodation: Fasting, postprandial and 
accommodation gastric volumes will be measured by 
single photon emission computed tomography 
(SPECT) (42) (Figure 7), which was developed and 
validated in our lab. 
Gastric Emptying: Gastric emptying (GE) will be 
measured by radioscintigraphy after overnight fast 
using a 111In radiolabeled meal consisting of 2 
scrambled eggs, one slice of whole wheat bread and 
one glass of skim milk (320kcal, 30% fat). Performance characteristics and normal values (214 female and 105 
male volunteers) are published (43). A variable region of interest program will be used to quantitate counts in 
the stomach. Data will be summarized as GE T1/2 and GE % emptied at 2 and 4 hours. Note that in healthy 
controls, gender, but not age or BMI, was associated with GE of solids (GE T1/2, proportion emptied at 1 hour 
and 2 hours, all p<0.001) (43).   
Table 2.  Mean + SD for gastric emptying (healthy adults) using the same method (43) 
  
All controls, n=319 
Male controls, n=104 
Female controls, n=215 
Age , y  
36.2 + 13.1 
34.6 + 13.3 
37.2 + 12.8 
BMI, kg/m2 
26.9 + 5.1 
27.8 + 4.5 
26.5 + 5.3 
Solid GE T1/2 
121.7 + 29.8 
109.9 + 28.6 
127.7 + 28.7 
Glucose monitoring in relation to measurement of GE: If the fasting glucose is >250mg/dl on either test 
day, diabetic subjects will be managed following standard of care in clinical setting. The recommended insulin 
doses will follow standard care: “Insulin sliding scale with Insulin regular: glucose 250-259 mg/dl = 3 units; 260-
299 mg/dl = 4 units; 300-339 mg/dl = 5 units; 340-379 mg/dl = 6 units; 380-399 mg/dl = 7 units; ≥400 mg/dl = 
call physician to assess subject and to determine continued progression of study activities.”  
Symptoms during GE study: We shall measure aggregate and individual symptom scores (nausea, bloating, 
fullness, pain) area under the curve (AUC) during the 4 hours after the standard meal during the GE test. 
 
Satiation  
Ensure® nutrient drink test (1kcal/mL, 11% fat, 73% carbohydrate, and 16% protein), which was 
developed and validated in our lab (44), with ingestion at a constant rate of 30ml/min will measure volume to 
Figure 7. SPECT measures gastric accommodation      


fullness (VTF) and maximum tolerated volume (MTV). Briefly, participants record their sensations every 5min 
using a numerical scale from 0 to 5, with level 0 being no symptoms, level 3 corresponding to fullness 
sensation after a typical meal, and level 5 corresponding to the MTV (maximum or unbearable 
fullness/satiation). Nutrient intake is stopped when subjects reach the score of 5. Postprandial symptoms of 
fullness, nausea, bloating, and pain are measured 30min after the meal using 100mm horizontal visual analog 
scales, with the words “none” and “worst ever” anchored at each end (Appendix 4). 
 
Patient Reported Outcomes (PROs): Symptoms during 4 Weeks of Randomized Treatment 
1. Assessment of upper gastrointestinal symptoms in patients with gastroparesis: ANMS GCSI-DD 
Every day, participants will fill in the GCSI-DD questionnaire (Appendix 5) (44) which covers the relevant 
symptoms from the patient’s perspective. It appraises 9 symptom severity items, which cover the following 
domains: nausea/vomiting (three items); fullness/early satiety (four items); and bloating (two items). The diary 
also contains items on the frequency of vomiting and retching, symptom severity items for upper abdominal 
pain and upper abdominal discomfort, and an overall rating of gastroparesis severity. Symptoms are rated by 
the patients from none (0) to very severe (5). The total GCSI-DD is calculated representing the mean of the 
three subscale scores of nausea/vomiting, postprandial fullness/early satiety, and bloating. Responsiveness of 
this instrument has been demonstrated by prospective assessment of 69 patients (46 idiopathic, 19 diabetic, 
and 4 post-fundoplication gastroparesis). Excellent test-retest reliability was seen for GCSI-DD scores, and 
there were significant correlations between GCSI-DD scores and clinician ratings of symptom severity. 
Responders to treatment reported improvements in nausea [effect size (ES) =0.42, P<0.001], postprandial 
fullness (ES=0.83, P<0.001), bloating (ES=0.34, P<0.001), and early satiety (ES=0.53, P<0.001), but there 
were lower responses for upper abdominal pain (ES=0.29) and vomiting (ES=0.22; P=0.119). Minimal 
important differences were estimated based on baseline to 4 weeks changes in symptom scores for small 
improvements. Minimal important differences were 0.55 for nausea, 0.97 for excessive fullness, 0.63 for 
bloating, 0.77 for postprandial fullness, and 0.30 for abdominal pain (45).  
Recent data also demonstrated GCSI-DD responsiveness in 
diabetic gastroparesis with treatment of the pentapeptide ghrelin 
agonist, relamorelin (46). Therefore, the GCSI-DD is a valid 
patient reported outcomes instrument for use in patients with 
gastroparesis, and demonstrates responsiveness to a prokinetic.   
2.  Assessment of upper gastrointestinal symptoms in 
patients with functional dyspepsia 
    As in a previous large, multicenter study of pharmacotherapy 
in functional dyspepsia (47) anchored at Mayo Clinic, we shall 
assess patient reported outcomes (PROs) using validated 
instruments:  
a.  Weekly global symptom assessment will be measured 
through adequate relief of dyspepsia symptoms during the prior 
week (48,49). This self-report measure is considered clinically relevant and has been tested for 
responsiveness in functional dyspepsia (50,51). 
b.  Disease-specific validated Nepean Dyspepsia Index (NDI) (Appendix 6) will be used to assess functional 
dyspepsia quality of life (52) at baseline and post-treatment. NDI scores are summarized as overall quality of 
life and 5 subscales: interference, knowledge/control, eating/drinking, sleep disturbance, work/study (range: 0 
to 100) (52). NDI also evaluates mean symptom scores for abdominal pain and postprandial distress. 
c.  Validated daily symptom diaries assessing upper abdominal pain, nausea, bloating, fullness, and early 
satiety on a scale of 0 to 3 (0 nil; 1 mild; 2 moderate; 3 severe) using a validated instrument (53) and simply 
tabulating the information.  
d. Leuven Postprandial Distress Scale (LPDS), the most validated symptom scale available with psychometric 
evidence supporting the LPDS’s individual items, as well as evidence of responsiveness to treatment (54-56), 
comprises eight symptoms (early satiation, postprandial fullness, upper abdominal bloating, epigastric pain, 
epigastric burning, nausea, belching and heartburn) with verbal descriptors rated for severity (0-4). The 
symptoms early satiation, postprandial fullness, and upper abdominal bloating constitute the most valid 
symptom group for postprandial distress in FD with an established minimal clinically important difference.  
e.  Functional Dyspepsia Symptom Diary (FDSD), a content-valid measure (57), with psychometric evidence 
supporting the FDSD’s individual items (stomach pain, stomach burning, nausea, bloating, stomach fullness, 


early satiety, burping/belching rating, burping/belching bothersome) measured on 11-point (0-10) scale and 
total score (stomach pain, stomach burning, bloating, stomach fullness, early satiety: maximum score of 50). 
Pharmacogenomics: Collection and storage of venous blood for DNA studies:  All participants in the 
trials in aim 1 will have 10mL venous blood sample for DNA extraction and storage. Genotyping of FAAH 
(rs324420), and CNR1 (rs806378) will be performed using TaqmanTM SNP Genotyping assays (Applied 
Biosystems Inc., Foster City, CA, USA) in accordance with the manufacturer’s instructions. 
Rationale for the selection of candidate cannabinoid genetic polymorphisms  
CNR1 (the gene for CB1 receptor) has 2 synonymous single nucleotide polymorphisms (SNPs), rs35057475 
and rs1049353; neither results in a change in amino acid sequence. There is an (AAT)n repeat at the 3’ end of 
CNR1, 18,000 bases downstream from the start site of exon 4 of CNR1. The number of repeats is highly 
variable (from 2 to 6 repeats) and, although associations with psychiatric disease, i.v. drug use, and response 
to antipsychotics have been described (58-62), the functional significance of this genetic variation is unclear. 
The T allele of CNR1 polymorphism rs806378 is associated with altered nuclear protein binding in an 
electrophoretic mobility shift assay, suggesting that rs806378 is a functional polymorphism (63). We 
previously demonstrated association of this genotype with gastric and colonic functions (see Background).  
FAAH 385C to A allelic variant (rs324420) leads to a Pro129Thr amino acid sequence change, which 
decreases expression of the FAAH protein due to reduced protein stability (64). The prevalence of the A allele 
is 16%–25% in studies of Caucasians in the NCBI database. Our laboratory has previously confirmed the A 
allele frequency to be 25% in our sample population of healthy controls and IBS patients in southeastern 
Minnesota (18). Reduction in FAAH protein level and activity compromises inactivation of the endocannabinoid 
anandamide, which leads to higher synaptic concentrations of anandamide and resulted in a greater effect of 
the exogenously administered cannabinoid agent, dronabinol, via activation of CB1 and CB2 receptors. 
In addition, we shall screen patients’ CYP3A4 and CYP2C19 genes, which impact the main CYP450 
enzymes responsible for cannabidiol metabolism (65). Ultra-rapid metabolizers for CYP2C19 [estimated 17% 
and 18% based on literature review (36)] will be excluded since this could impact assessment of effects of 
cannabidiol.    
 
General Approach for Statistical Analyses   
The analyses will be based on a 2-treatment design to compare the effects of each medication tested and 
placebo on post-treatment gastric functions, satiation, incretins and symptoms. The analyses will use a 2-way 
analysis of covariance (ANCOVA) model with treatment as the quantitative trait, and a treatment by 
quantitative trait interaction term. It is anticipated that all primary and secondary endpoints will be normally 
distributed. If the data are not normally distributed, we shall use an empirical normal quantile transformation 
also known as the van der Waerden normal scores (66,67), or the generalized linear mixed models (GLMM) 
that provides a rich class of statistical models to model correlated data with responses from the exponential 
family of distributions including Gaussian, Binomial, Poisson among others (68). Covariate analysis may be 
conducted using gender and BMI as covariates, since these may significantly affect gastric functions such as 
satiation maximum tolerated volume, and using smoking and gender as covariates, since these may 
significantly affect drug levels of secretin. Symptom relief in aim 2b will be evaluated for treatment effects using 
a logistic regression model, with adequate relief as the binary dependent variable (responder definition based 
on at least 50% of weeks of symptom relief).  
Analysis: Primary endpoints for this study will be: 
- 
Fasting gastric and accommodation volumes measured by SPECT 
- 
Volume to fullness (VTF, mL) on satiation test  
- 
Gastric emptying T1/2 of solids on scintigraphy  
- 
Average weekly GCSI-DD score on treatment in patients with gastroparesis 
- 
Postprandial distress score on Nepean Dyspepsia Index in patients with functional dyspepsia   
Secondary endpoints will be: 
- 
Absolute postprandial gastric volume by SPECT 
- 
Gastric emptying of solids at 2h and 4h on scintigraphy 
- 
Aggregate symptoms and individual symptom scores (nausea, bloating, fullness, pain) area under the 
curve (AUC) during the 4 hours after the standard meal during the gastric emptying test 
- 
Maximum tolerated volume (MTV) and aggregate symptoms score 30min after MTV on satiation test  
- 
Individual symptom scores (nausea, bloating, fullness, pain) on satiation test 
- 
Individual subscales of GCSI-DD (3 subscales: nausea/vomiting, postprandial fullness/early satiety, and 
bloating) in patients with gastroparesis (aim 1a)  


- 
Overall Nepean Dyspepsia Index (NDI) score in functional dyspepsia (aim 1b) 
- 
Abdominal pain score on NDI in functional dyspepsia (aim 1b) 
- 
Proportion of responders based on adequate relief in functional dyspepsia (aim 1b) 
- 
Average daily aggregate symptom score for upper abdominal pain, nausea, bloating, fullness, and early 
satiety (each on a scale of 0 to 3) in functional dyspepsia (aim 1b) 
LPDS score and FDSD scores will be exploratory endpoints since they have only recently been validated. 
Sample Size Assessment   
     
This is based on results of the primary endpoints in our Mayo Clinic lab. Expected (80% power, α=0.05, 
assuming parallel-group study and unpaired analysis with n=22 in aim 1a and n=24 aim 1b) demonstrable 
differences compared to placebo show that the study is powered to detect clinically relevant effects of 
cannabidiol based on the variation (SD) observed from our Mayo prior studies (42-44,46,47). 
TABLE 3. Sample Size Assessment:  Response 
Mean SD 
Effect size detectable (absolute [% of 
mean],  n=24 per group  
Fasting gastric volume, mL 
273 
57 
47mL (17%) 
Postprandial gastric volume, mL 
848 
111 
91.7mL (10.8%) 
Gastric emptying of solids T1/2, min 
122 
29.8 
24.62 (20.2%) 
Volume to fullness, mL 
755 
330 
273mL (36.2%) 
Maximum tolerated volume, mL 
1283 
400 
330.5mL (25.8%) 
Δ from baseline in average (of 3 subscales in) GCSI-DD  
-1.4 
0.5 
0.413 (29.5%) 
Average Aggregate Symptoms Score for dyspepsia  
1.42 
0.64 
0.50 (35.2%) 
NDI overall quality of life score 
63.6 
22.5 
18.6 (29.2%) 
NDI abdominal pain score 
29.4 
10.4 
8.6 (29.3%) 
NDI postprandial distress score 
12.8 
7.5 
6.2 (48.4%) 
    Therefore, the study has sufficient power to detect clinically relevant effects on quantitative traits. The study 
will provide important information on the mean response in clinically important endpoints in the two trials and, 
therefore, provide important preliminary information, such as coefficient of variation of the response in the 
current hypothesis-generating trials in order to plan future hypothesis-testing trials. 
 
Interim Analysis: As part of an on-going method to compare the effects of each medication tested and 
placebo, an interim analysis will be conducted when 50% of the first specific aim has been reached.  
 
Rationale for Interim Analysis:  
a. To assess power of the study based on the actual coefficient of variation as measured in the actual study 
with >50% completed; this is because the coefficient of variation could be different from the COV used in the a 
priori power calculation used in development of the protocol.  
b. As part of the analysis, the statisticians will also provide a comparison of the results on the primary and 
secondary endpoints; this assessment will be communicated to the investigators as average data (e.g. median 
and IQR) for the treatment GROUPS rather than individual patient data. These group data could be used for 
preparation of preliminary reports in the form of abstract for national meetings specifically, Digestive Disease 
Week to be held in May 2021 for which the deadline for abstract submission is December 1, 2020. 
c. As a result of the power analysis, it is possible that the sample size may be either reduced or increased or 
the study could be stopped because of “futility” if there is no evidence of a trend to suggest efficacy of 
treatment. 
 
Outcome of Interim Analysis: 
In accordance with the approval from IRB to conduct an interim analysis after 50% of planned participants with 
gastroparesis had completed the study activities according to protocol, the data of 24 patients (that is 50% of 
the number originally proposed for the study) were analyzed by the study statistician, W Scott Harmsen MS.  
 
The objective of the interim analysis is to determine what is the SAMPLE SIZE (currently planned at 24 per 
treatment arm, that is cannabidiol vs placebo, 1:1 ratio) required, based on the current data (group difference 
and coefficient of variation) to demonstrate EFFICACY based on the STATED PRIMARY endpoints in the NIH 
grant application: 
 
Primary endpoints: Physiological traits and patient reported outcomes for cannabidiol vs. placebo groups:  
(a). Gastric emptying T1/2 solids 


(b). Fasting and accommodation gastric volumes  
(c). Satiation by the maximum (max) tolerated volume 
(d). Average daily (total) GCSI-DD score 
 
Secondary endpoints:  
1. Satiation assessed by the volume to fullness 
2. Aggregate symptom score 30 min. after max. tolerated volume 
3. GCSI-DD subscores of: nausea, vomiting, postprandial fullness, satiety, bloating, pain 
 
Data Included in Interim Analysis:  Among these 24 patients with documented diagnosis of gastroparesis, 
one randomized patient did qualify as the baseline gastric emptying was within the normal range at the time of 
this study.  Therefore, data from 23 patients were included in the analysis.  Physiological measurements at end 
of treatment were unavailable in 2 patients (one developed COVID infection, one had a family emergency). 
The summary data were provided by the study statistician, but the study blind was maintained and 
randomization code was only provided to the statistician from the research pharmacy. Gastric emptying T1/2 
values were censored to a maximum of 240 minutes since this was the last time point of data collection. The 2 
groups were well-matched at baseline. 
 
Data show median (IQR) 
Cannabidiol 
Placebo 
P value 
N (F and M) 
10 (9 and 1)  
13 (12 and 1) 
1.0 
Age (y) 
45.3 (32, 57) 
44.5 (36, 55) 
0.93 
BMI (kg/m2) 
26.1 (20.7, 29.1) 
27.3 (25.7, 32,2) 
0.42 
Baseline GE T1/2, min 
208.2 (140.8, 
240) 
198.4 (172.5, 
230.3) 
0.88 
Baseline GE lag time, min 
84.5 (65.0, 
111.8) 
73.6 (64.0, 101.3) 
0.64 
Baseline feeling excessively full score 
2.0 (2.0, 3.0) 
2.0 (1.0, 2.0) 
0.58 
Baseline upper abdominal pain score 
1.2 (0.8, 2.0) 
1.0 (0.8, 1.8) 
0.95 
Baseline # vomiting episodes 
(maximum 5) 
0.0 (0.0, 1.0) 
0.0 (0.0, 1.0) 
0.60 
Baseline average GCSI-daily diary 
score 
1.8 (1.4, 2.4) 
1.2 (0.8, 1.8 
0.29 
  
Sample Size re-estimation based on the observed SD  
To observe statistically significant differences in effects of cannabidiol and placebo with 80% power, the interim 
analysis shows the following changes relative to baseline (baseline MINUS end of treatment values shown) in 
the 2 treatment arms, conditional power and estimated number of patients required in each treatment arm: 
 
 
Placebo 
Cannabidiol 
 
 
 
 
Measurement 
 
Mean 
 
SD 
 
Mean 
 
SD 
 
T-
stat 
Conditional 
Power 
Sample 
Size Re-
est. (n1=n2) 
Analyzed using ANCOVA for Change in measure Baseline to Post-Tx 
∆ TrGEt50LinearMax240 
16.4 
26.8 
-7.7 
48.9 
-
1.50 
0.61 
38 
∆ Total GCSI Sx scores 
(Q’s 1 to 5) 
0.1 
0.4 
0.6 
0.8 
1.84 
0.85 
22 
∆ Daily Q3 Feel excess full 
0.2 
0.6 
0.5 
0.6 
0.93 
0.80 
64 
∆ Daily Q4 Upper 
Abdominal Pain 
0.0 
0.8 
0.6 
1.1 
1.50 
0.62 
37 
∆ Daily Q5 # Vomit (max=5) 
-0.2 
0.6 
0.8 
1.5 
2.16 
0.93 
15 
Measurements without a Baseline measure 
Nutrient Drink max tolerated 
Kcal 
639.5 
286.7 
856.3 
343.7 
1.65 
0.71 
30 
Nutrient Drink Kcal to 
fullness 
384.6 
200.7 
506.6 
236.3 
1.34 
0.49 
47 


 
Based on ∆ values, a positive number indicates an improvement in the parameter on treatment relative to 
baseline.  A priori, conditional power of <0.20 was identified as indicative of futility to continue the trial.  Given 
that several parameters of interest were associated with conditional power >0.20, and the sample size required 
to identify clinically important differences with n<24 per treatment group (which was originally planned in study 
protocol), the conclusions reached following the interim analysis were: 
 
1. To continue the clinical trial with the same treatments (cannabidiol and placebo) 
2. Reduce total sample size from 48 to 44 
3. Retain strategies of concealed allocation, study blind of all investigators on the study 
With larger sample size in the two treatment groups, it is conceivable that the SD and coefficient of variation 
will be smaller in the final study database, thereby providing potential to appraise other endpoints shown in the 
table, such as upper abdominal pain, maximum tolerated kcal, and GE T1/2.  
 
Subsequent Interim Analysis:  As part of an on-going method to compare the effects of each 
medication tested and placebo, a subsequent interim analysis will be conducted when >85% of 
the gastroparesis group participants have completed study procedures.  
 
Rationale for Subsequent Interim Analysis:  
The objective of the interim analysis is not to change the current goal of evaluating 44 patients 
randomized to either cannabidiol or placebo as is currently detailed in the statistical analysis plan and 
was confirmed following an interim analysis performed for the purposes of evaluating statistical power 
and appropriate sample size. 
This subsequent interim analysis is intended to provide an evaluation of data collected from more than 
85% of the gastroparesis group participants.  In this analysis, statisticians will provide a comparison of 
the results on the primary and secondary endpoints; this assessment will be communicated to the 
investigators as average data (e.g. median and IQR) for the treatment GROUPS rather than individual 
patient data in order for the investigators to remain blinded to the individual participant data and to the 
treatment group to which each individual had been assign by randomization. These group data would 
be used for preparation of preliminary reports in the form of abstract for national meetings, specifically 
Digestive Disease Week to be held in May 2023, for which the deadline for abstract submission is 
December 1, 2022. 
 
Approval of this request for the subsequent interim analysis is necessary for the research pharmacy to 
send the randomization code exclusively to the statistician. 
 
 
 
APPROACH  
AIM 1a:  Effects of treatment with cannabidiol on gastric functions, satiation and symptoms in patients 
with gastroparesis  
Hypothesis 1a:  Cannabidiol enhances gastric accommodation and reduces post-nutrient challenge 
symptoms without altering gastric emptying in patients with gastroparesis.  
Specific Aim 1a:  To compare effects of cannabidiol vs. saline on satiation, fasting gastric volume, gastric 
accommodation and emptying, and GCSI-DD in patients with gastroparesis 
Rationale:  Cannabidiol has multiple effects on GPCRs, 5-HT1a receptors and neuroprotection to potentially 
impact gastric functions and pain in patients with gastroparesis. Pain is a significant unmet need in patients 
with gastroparesis. In the NIH Gastroparesis Consortium Patient Cohort, the predominant symptoms in 393 
patients were pain/discomfort in 21% and nausea/vomiting in 44%. Pain was rated moderate or severe in 66% 
of those with pain. Idiopathic gastroparesis (256 patients) was correlated with opioid and antiemetic use, 
depression, anxiety, and poor QOL. Pain presentation was also not associated with the results of gastric 
emptying test, or with diabetic neuropathy or control of diabetes (69). 


Experimental design:  We will perform a randomized, double-blinded, placebo-controlled study of 
cannabidiol, 20mg/kg/day (achieved after dose escalation), and placebo, each in two divided doses with n=22 
per treatment arm. All participants will have gastroparesis symptoms, prior documentation of delayed gastric 
emptying (GE) at Mayo Clinic, and will undergo baseline measurements of GE to be used as a covariate in 
assessing the response to treatment with cannabidiol. 
Randomization will be stratified on gender and BMI. 
Experimental procedures and measurements:   All 
participants will undergo measurements of GE of solids, gastric 
volume (fasting and postprandial), Ensure® nutrient drink 
satiation test (which also serves as a dyspeptogenic meal) and 
symptom assessment.  
Details of each are provided in the Common Methods section.              
Statistical analysis: ANCOVA will be used to compare the 2 
treatment groups, including baseline GE T1/2 as covariate. 
Primary endpoints: Physiological traits and patient reported 
outcomes for cannabidiol vs. placebo groups:  
(a). Gastric emptying T1/2 solids 
(b). Fasting and accommodation gastric volumes  
(c). Satiation by the maximum (max) tolerated volume 
(d). Average GCSI-DD score 
Secondary endpoints:  
1. Satiation assessed by the volume to fullness 
2. Aggregate symptom score 30 min. after max. tolerated volume 
3. GCSI-DD subscales: nausea/vomiting, postprandial fullness/satiety, bloating 
Statistical power: Addressed in the Common Methods/Statistics section 
Anticipated results compared to placebo:  
a. Cannabidiol will increase fasting and accommodation gastric volumes, and calorie intake at satiation test 
without significantly retarding gastric emptying. 
b. Cannabidiol will reduce average weekly symptoms score based on GCSI-DD.   
c. We anticipate <5% dropouts due to medication intolerance or adverse events in this single-center study, 
consistent with experience from multicenter studies conducted in patients with syndromic seizures.  
Potential pitfalls, precautions taken, and alternative strategies: 
a. Feasibility: Given our 100-person database of patients with gastroparesis residing within 150 miles of 
Rochester, MN and with prior documentation of upper gastrointestinal symptoms consistent with gastroparesis, 
as well as documented delay in gastric emptying, we are confident that we can recruit the required number of 
participants for the studies that involve only noninvasive tests. 
b. Consideration of sex as a biological variable: In our past cohort of 100 patients, 69% were female. 
Therefore we anticipate recruitment of 44patients will include sufficient numbers of male and female patients.  
c. Scientific premise for inclusion of both genders: Although gastroparesis and functional dyspepsia are more 
prevalent in females, there is no a priori evidence that the effect of cannabidiol differs between genders and 
the pathophysiological mechanisms do not appear to be different between genders. Therefore, our study will 
assess treatment efficacy in both genders; we shall recruit numbers of men and women in ratio of 1:1.5.   
d. Drop-outs: The hypothesis-testing study will utilize intention-to-treat principles. The analysis population will  
include all randomized subjects. We plan to include in the informed consent forms clear information to 
differentiate treatment discontinuation from study withdrawal, as well as a statement educating patients about 
the continued scientific importance of their data, even if they discontinue study treatment early. Therefore, 
patients will be followed after treatment discontinuation in order to preserve the ability to analyze endpoints for 
all participants who underwent randomization and, thus, to make possible intention-to-treat inferences (70). 
e.  Missing data: We shall explore three methods for data imputation: 
    (i)  Imputation of any missing data for the primary endpoint (e.g. gastric emptying T1/2) will use the overall 
mean T1/2 for all subjects randomized, adjusting the error degrees of freedom (df) in the ANCOVA model by 
subtracting one df for each value imputed to provide a more accurate estimate of residual error variance.  
   (ii)  Using a mixed-model repeated measures method, we shall assume that continuous repeated measures 
have a normal distribution with a specified form of mean and covariance matrix. With multiple imputations, 
multiple sets of plausible values for missing data will be created from their model-based predictive distribution, 
and estimates and standard errors will be obtained using multiple-imputation combining rules (50). 
Figure 9. Experimental protocol to compare 
the effects of cannabidiol and placebo in 
gastroparesis   


  (iii)  We shall use the last rank carried forward (LRCF) approach as described in O’Brien et al. (71).  
     In order to develop pre-specified monitoring and analysis plans, we shall establish a DATA SAFETY 
MONITORING PLAN which will involve review by experts independent of the study, using a team comprised of 
researchers with track records in biostatistics and clinical trials and expertise in the quantitative traits. We have 
established definite stopping rules for the trial. 
Significance: This study will evaluate efficacy, safety, and mechanisms of action of cannabidiol in the largest 
single-center study to date, and it will provide information on the coefficient of variation in patient reported 
outcomes to plan future hypothesis-testing, multicenter studies of the effects of cannabidiol in gastroparesis.  
 
AIM 1b:  Acute effects of cannabidiol on gastrointestinal functions and symptoms in patients with 
functional dyspepsia and non-delayed gastric emptying  
Hypothesis 1b:  Cannabidiol enhances gastric accommodation and reduces post-challenge symptoms without 
altering gastric emptying in patients with functional dyspepsia with non-delayed baseline gastric emptying.  
Specific Aim 1b:  To compare the effects of cannabidiol vs. placebo on satiation, fasting gastric volume, 
gastric accommodation and emptying, and symptoms in patients with functional dyspepsia with normal 
baseline gastric emptying, 
Rationale: A prominent pathophysiologic feature of functional dyspepsia is defective gastric accommodation, 
with inadequate relaxation of the fundus of the stomach in response to eating, which is responsible for the 
post-cibal pain. This was observed in 47% of 151 patients with functional dyspepsia in a Mayo Clinic study 
performed in the clinical practice of the PI (72). There are presently no generally effective medications to 
restore normal gastric accommodation, and there is only limited support, based on single-center studies, for 
use of such diverse medications as clonidine, 
sumatriptan, buspirone (many of which have central 
or vascular side effects), or for acotiamide, a 
cholinesterase inhibitor, approved for use in Japan, 
but not in the USA. 
Experimental design: We shall perform a 
randomized, double-blinded, placebo-controlled study 
of cannabidiol. b.i.d., and placebo, b.i.d., with n=24 
per treatment arm. All participants will have a history 
of functional dyspepsia with prior documentation of 
normal or accelerated gastric emptying at Mayo Clinic 
and will undergo baseline measurements of gastric 
emptying to be used as a covariate in assessing the 
response to treatment with cannabidiol. 
Randomization will be stratified on gender, and BMI.  
Experimental procedures and measurements:  All participants will undergo gastric emptying of solids, 
gastric volume (fasting and postprandial), satiation test (which also serves as a dyspeptogenic meal), 
symptoms assessment. Details of each are provided in the Common Methods section. 
Statistical analysis: ANCOVA will compare the 2 treatment groups, including baseline gastric emptying T1/2 as 
covariate. The endpoints of the study will be the same as in specific aim 1a, with the exception that 
symptoms/patient response outcomes will be based on proportion of average weekly adequate relief 
responders, NDI and daily symptom scores over the 28-day treatment trial, as in Common Methods section.  
Statistical power: See Methods/Statistics section 
Anticipated results compared to placebo: Cannabidiol will increase fasting and accommodation gastric 
volumes and calorie intake at satiation test without significantly retarding gastric emptying. Cannabidiol will 
increase the proportion of responders with at least 50% weeks with reported adequate relief, QOL scores and 
abdominal pain scores based on NDI at end of 4 weeks of treatment compared to baseline. 
Potential pitfalls, precautions taken, and alternative strategies: 
a. Feasibility: Given the community prevalence of functional dyspepsia and the review of medical records 
which identified >250 patients with functional dyspepsia symptoms without delayed gastric emptying seen in 
the past 5 years at Mayo Clinic (37), we are  confident that we can recruit the required number of participants 
for the studies that involve only noninvasive tests. 
b. Consideration of sex as a biological variable: In the ~1270 person database, 60% were female (37). We 
anticipate a female to male ratio of 1.5:1 to ensure we can assess sex as a biological variable.  
Figure 10. Experimental protocol 
 


c. Scientific premise for inclusion of both genders includes: Although functional dyspepsia is more prevalent 
in females, there is no a priori evidence that the effect of cannabidiol differs between genders, and the 
pathophysiological mechanisms do not appear to be different between genders. Therefore, our study will 
assess treatment efficacy in both genders, and we shall recruit ~ equal numbers of men and women. 
d. Drop-outs and missing data will be managed as for specific aim 1a.  
Significance: This study will evaluate efficacy, safety, and mechanisms of action of cannabidiol in the largest 
single-center study in functional dyspepsia to date, and it will provide information on the coefficient of variation 
in patient reported outcomes to plan future hypothesis-testing, multicenter studies of the effects of cannabidiol 
in patients with functional dyspepsia.  
 
Aim 2: Treatment by genotype interaction of cannabidiol and FAAH and CNR1 genes and gastric 
functions in patients with functional dyspepsia or gastroparesis 
Hypothesis 2: FAAH rs324420 and CNR1 rs806378 genotype significantly affect the response of gastric 
accommodation, gastric emptying and satiation to treatment with cannabidiol in patients with gastroparesis or 
functional dyspepsia with normal baseline gastric emptying.  
Specific Aim 2: To assess pharmacogenetics effects of variants in FAAH and CNR1 genes on the 
pharmacodynamics effects of cannabidiol vs. placebo on gastric accommodation, gastric emptying and 
satiation in the same patients with gastroparesis or functional dyspepsia. 
Rationale: In prior studies, FAAH rs324420 and CNR1 rs806378 gene variants were associated with gene by 
treatment interactions on diverse gastrointestinal motor functions in response to the non-selective cannabinoid 
agonist DRO (see background). Genotype distributions (18,19) in participants in prior Mayo Clinic studies are 
shown in Figures 11 and 12. We have previously demonstrated 
(18,19) the MAFs of the FAAH and CNR1 
variants in our catchment population are 
consistent with NCBI and other literature 
reports with FAAH MAF of 0.25 and CNR1 
MAF of 0.29. 
Experimental design: From specific aim 1, 
there will be 46 patients (22 with 
gastroparesis and 24 with functional 
dyspepsia) treated with cannabidiol; we 
shall compare in these patients the 
association of gene variants on the effects 
of cannabidiol on gastric emptying using a 
dominant genetic model. The model will 
include gender, treatment (yes/no 
cannabidiol), gene variants, plus the 
interaction gene x treatment.  
Experimental procedures and measurements: All participants will have undergone gastric emptying of 
solids, gastric volume (fasting and postprandial) and satiation test in specific aim 1.  Genotyping for FAAH 
rs324420 and CNR1 rs806378 and CYP 3A4 and 2C19 will be performed.  See common methods section. 
Endpoints: (a) Gastric emptying T1/2 solids; (b) Accommodation gastric volume; (c) Satiation by the MTV 
Statistical considerations and analysis:  
Applying the dominant genetic model, we anticipate there will be a 60:40 split of FAAH rs 324420 CC vs. 
CA/AA, and a 50:50 split for CNR1rs806378 CC vs. CT/TT. 
Given there will be 46 participants receiving cannabidiol and assuming an approximate 50:50 split of the 
participants based on both genotypes (that is, 23 patients CC vs. 23 CA/AA FAAH rs 324420 or 23 CC vs. 23 
CT/TT for CNR1 rs806378), we anticipate the following effect sizes attributable to the gene variants (Table 4): 
Table 4.  Response 
Mean 
SD 
Effect size detectable ([% of mean],  n=24/ genotype group  
Fasting gastric volume, mL 
273 
57 
47mL (17%) 
Postprandial gastric volume, mL 
848 
111 
91.7mL (10.8%) 
Gastric emptying solids T1/2, min 
122 
29.8 
24.62 (20.2%) 
Volume to fullness, mL 
755 
330 
273mL (36.2%) 
Maximum tolerated volume, mL 
1283 
400 
330.5mL (25.8%) 
ANCOVA will compare the genotypes for each gene variant, including baseline GE T1/2 as covariate.  
Figure 11: FAAH rs324420 genotype 
distribution in FGID and healthy 
controls studied at Mayo Clinic and 
reported distribution in NCBI and in 
a study mostly in Caucasians. 
Figure 12: CNR1  
rs806378 genotype 
distribution in FGID 
and healthy controls  at 
Mayo Clinic (mostly 
Caucasians)


Anticipated results: Effect of cannabidiol will be significantly associated with FAAH and CNR1 genotypes 
consistent with the hypothesis that the gene variants impact the function of the receptor target or the 
inactivation of endocannabinoids that modulate gastric motor functions, or calorie intake at satiation test.  
Potential pitfalls, precautions taken, and alternative strategies: 
Feasibility: The study participants will be enrolled in specific aim 1; the power calculation based on our patient 
community gene minor allele frequency shows that the study has sufficient power to detect clinically relevant 
gene * treatment interactions.  
Genetic variation in metabolism (inactivation) of cannabidiol: Ultra-rapid metabolizers for CYP2C19 [estimated 
17% and 18% based on literature review (36)] will be excluded since this could impact assessment of effects of 
cannabidiol.    
Consideration of sex as a biological variable: In the ~1270 person database, 60% were female (37). We 
anticipate a female to male ratio of 1.5:1 to ensure we can assess sex as a biological variable.  
Scientific premise for inclusion of both genders includes: Although functional dyspepsia is more prevalent in 
females, there is no a priori evidence that the effect of cannabidiol differs between genders, and the 
pathophysiological mechanisms do not appear to be different between genders. Therefore, our study will 
assess treatment efficacy in both genders, and we shall recruit men and women in the ratio 1:1.5. 
Drop-outs and missing data will be managed as for specific aim 1.  
Significance: This study will evaluate impact of common functional genetic variants in CB1 receptor and 
cannabinoid inactivation on the pharmacodynamics responses to cannabidiol, potentially important in 
individualizing therapy with cannabidiol in the treatment of gastroparesis and functional dyspepsia that may 
impact plan and design of future hypothesis-testing, multicenter studies of the effects of cannabidiol in patients.  
Overall Significance of Application: The proposed studies provide the ability to validate a recently approved 
pharmaceutical grade cannabidiol for the treatment and addressing the unmet need of millions of American 
citizens with gastroparesis or functional dyspepsia, including personalization of treatment based on genotype 
by treatment interactions.  This research team is uniquely poised to deliver on this vision.    
 
Time Table:      Years 1-4: specific aims 1, 2;   Year 5: data analysis and publications 


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in gastroparesis. J Clin Gastroenterol 2013;47:757-761 
 
74.  Minocha A, Chad W, Do W, Johnson WD. Racial differences in epidemiology of irritable bowel syndrome 
alone, un-investigated dyspepsia alone, and "overlap syndrome" among african americans compared to 
Caucasians: a population-based study. Dig Dis Sci 2006;51:218-226 
 
75.  Khemani D, Camilleri M, Roldan A, Nelson AD, Park S-Y, Acosta A, Zinsmeister AR. Opioid analgesic use 
among patients presenting with acute abdominal pain and factors associated with surgical diagnoses.  
Neurogastroenterol Motil 2017;29:e13000 
 
 

ICF_000.pdf: 
 
 
Pharmacodynamics, Pharmacogenetics, Clinical 
Efficacy and Safety of Cannabidiol for 
Gastroparesis and Functional Dyspepsia   
 
NCT03941288 
 
April 27, 2022 


 
 
Approval Date:  
April 27, 2022 
Not to be used after: March 22, 2023 
 
 
IRB#: 19-002483 00 
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Name and Clinic Number 
RESEARCH PARTICIPANT CONSENT AND PRIVACY 
AUTHORIZATION FORM 
 
Study Title:  Pharmacodynamics, Pharmacogenetics, Clinical Efficacy and Safety of 
Cannabidiol for Gastroparesis and Functional Dyspepsia   
 
IRB#:  
19-002483  
 
Principal Investigator: Dr. Michael Camilleri and Colleagues 
 
 
Key Study Information 
 
 
This section provides a brief summary of the study.  It is important for you to understand why 
the research is being done and what it will involve before you decide.  Please take the time to 
read the entire consent form carefully and talk to a member of the research team before 
making your decision.  You should not sign this form if you have any questions that have not 
been answered. 
It’s Your Choice 
 
This is a research study.  Being in this research study is your choice; 
you do not have to participate.  If you decide to join, you can still stop 
at any time.  You should only participate if you want to do so. You 
will not lose any services, benefits or rights you would normally have 
if you choose not to take part. 
Research Purpose 
 
The purpose of this research is to compare the effects of a cannabidiol 
medication versus placebo on stomach function in people with 
gastroparesis (a paralyzed stomach) and people with dyspepsia (an 
upset stomach caused by improper functioning of the stomach's 
muscles or nerves). 
 
You have been asked to take part in this research because you have 
been diagnosed with either gastroparesis or functional dyspepsia. 
What’s Involved 
 
Study participation involves comparing the effects of a cannabidiol 
medication versus placebo on stomach function in people with 
gastroparesis or dyspepsia. Study participation may last about 10 
weeks from the date of the first visit to the end of the study.  
 
Participants will undergo testing including gastric emptying, nutrient 
drink, gastric volume, as well as having blood samples drawn. 


 
 
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April 27, 2022 
Not to be used after: March 22, 2023 
 
 
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Participants will be randomized to either cannabidiol or placebo, 
which will be taken for 5 weeks. Participants have a 50 percent chance 
of receiving placebo instead of cannabidiol medication.  
Key Information 
Possible side effects of cannabidiol include rash, diarrhea, a decrease 
in appetite, sleep disturbance, and increase risk of infections, suicidal 
thoughts and behaviors, and elevated liver enzymes. You will also be 
exposed to radiation during the Gastric Emptying and Gastric Volume 
test, but the amount of radiation that you receive has a low risk of any 
harmful effects. Others with gastroparesis and functional dyspepsia 
may benefit in the future from what we learn in this research study. 
This research study is voluntary and you may choose not to take part 
in this study. 
 
Cannabidiol is a liquid taken by mouth, and it was recently approved 
by FDA for use in patients with a seizure disorder. It may reduce pain 
arising from internal organs such as the stomach.  
Learn More 
If you are interested in learning more about this study, read the rest of 
this form carefully. The information in this form will help you decide 
if you want to participate in this research or not.  A member of our 
research team will talk with you about taking part in this study before 
you sign this form.  If you have questions at any time, please ask us.    
 
 
 


 
 
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Not to be used after: March 22, 2023 
 
 
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Name and Clinic Number 
 
 
Making Your Decision 
 
 
Taking part in research is your decision.  Take your time to decide.  Feel free to discuss the study 
with your family, friends, and healthcare provider before you make your decision.  Taking part in 
this study is completely voluntary and you do not have to participate. 
 
If you decide to take part in this research study, you will sign this consent form to show that you 
want to take part. We will give you either a printed or electronic copy of this form to keep.  A 
copy of this form will be put in your medical record. 
 
For purposes of this form, Mayo Clinic refers to Mayo Clinic in Arizona, Florida and Rochester, 
Minnesota; Mayo Clinic Health System; and all owned and affiliated clinics, hospitals, and 
entities. 
 
 


 
 
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Not to be used after: March 22, 2023 
 
 
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Name and Clinic Number 
 
 
Contact Information 
 
If you have questions about … 
You can contact … 
 Study tests and procedures 
 Materials you receive 
 Research-related appointments  
 Research-related concern or complaint 
 Research-related injuries or emergencies 
 Withdrawing from the research study 
 
Principal Investigator: Dr. Michael Camilleri 
Phone: (507) 266-2305 
 
Study Team Contact: Maggie Breen-Lyles 
Phone: (507) 293-0237 
 
Ann Taylor 
Phone: (507) 266-3421 
 
 
Deb Eckert RN 
Phone: (507) 538-5860 
 
Monique Torres  
Phone: (507) 538-6599 
 
Irene Busciglio 
Phone: (507) 266-6615 
 
Institution Name and Address: 
Mayo Clinic 
200 First Street SW 
Rochester, MN 55905 
 Rights of a research participant 
 
Mayo Clinic Institutional Review Board (IRB)  
Phone: (507) 266-4000 
Toll-Free: (866) 273-4681 
 Rights of a research participant 
 Any research-related concern or complaint 
 Use of your Protected Health Information 
 Stopping your authorization to use your 
Protected Health Information 
 Withdrawing from the research study 
Research Subject Advocate (RSA) 
(The RSA is independent of the Study Team)  
 
Phone: (507) 266-9372 
Toll-Free: (866) 273-4681 
E-mail: researchsubjectadvocate@mayo.edu 


 
 
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April 27, 2022 
Not to be used after: March 22, 2023 
 
 
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Name and Clinic Number 
If you have questions about … 
You can contact … 
 Billing or insurance related to this research 
study 
Patient Account Services 
Toll Free: (844) 217-9591 
 
Other Information:   
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
 
 
Why are you being asked to take part in this research study? 
 
 
You are being asked to take part in this research study because you have been diagnosed with 
gastroparesis (a paralyzed stomach) or functional dyspepsia (an upset stomach caused by 
improper functioning of the stomach's muscles or nerves). 
 
 
Why is this research study being done? 
 
 
This research will compare the effects of a cannabidiol medication versus placebo on stomach 
function in people with gastroparesis (a paralyzed stomach) and people with dyspepsia (an upset 
stomach caused by improper functioning of the stomach’s muscles or nerves. 
 
 
Information you should know 
 
 
Who is Funding the Study? 
The National Institutes of Health is funding the study. The National Institutes of Health will pay 
your study doctor or the institution to cover costs related to running the study. 
 
Information Regarding Conflict of Interest: 
There are no individual or institutional conflicts of interest related to this study. 
 
 
 


 
 
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How long will you be in this research study? 
 
 
You will be in this study for about 10 weeks from the date of the first visit to the end of the 
study. This includes the screening and baseline visits, the study medication period, and end of 
study visits. 
 
 
What will happen to you while you are in this research study? 
 
 
If you agree to be in the study, you will be asked to participate in the following:  
 
Screening visit:  
You will come to the Clinical Research Trials Unit (CRTU) on Charlton 7, fasting is not 
required.  
 
After discussing the study and having a chance to have your questions answered, you will be 
asked to sign the informed consent form. During this visit, we will give you some questionnaires 
and review your medical history to see if you are eligible to take part in this research study. The 
Study Physician will review the results. If you aren’t eligible, we will tell you why.   
 
At this visit we will: 
• Ask you about your medical history and current medications or supplements 
• Perform a physical exam, including measuring your height, weight, and “vital signs” 
(blood pressure, temperature, heart and breathing rates) 
• Females of child-bearing potential will be asked to have a urine pregnancy test which 
must be negative 
• Ask you to complete questionnaires about your general health and well-being and any 
bowel issues you have experienced during the past year 
• Draw a blood sample to check on your ability to receive the medication safely and for 
DNA (genetic testing). 
• The study physician will decide if you need any additional blood/urine tests to determine 
your eligibility 
• Provide you with a study schedule of visits 
 
This visit will last approximately 1 to 1.5 hours. 
 
 


 
 
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Baseline Visits:  
You will have the following test done. The Gastric Emptying test and Medication Dispense visit 
can be combined on the same day.  If you have not previously completed a Gastric Emptying 
test, your baseline Gastric Emptying test may be used to determine eligibility and can be 
combined with your screening visit. 
 
Baseline Gastric Emptying Test: You will come to the CRTU after an 8 hour fast (nothing to 
eat or drink prior to your visit).  Refrain from alcohol use for 48 hours prior to testing.  Refrain 
from caffeine (e.g., tea, coffee, energy drinks, and caffeine-containing sweets) for 24 hours 
before and until the end of testing.  Notify the study team in advance if you have any food 
allergies or intolerances. Diabetic volunteers should bring their own insulin medications and 
supplies. 
At this visit we will: 
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must be negative) within 48 hours prior to this test.   
• Measure your “vital signs” (blood pressure, temperature, heart and breathing rates) 
• Measure your height and weight 
• Test your fasting blood glucose by sticking your finger for a drop of blood, if you are 
diabetic 
• Administer the Gastric Emptying Test: The test involves eating a 320 kcal meal of 
scrambled eggs, 1 slice of bran bread toast and 1 cup of skim milk within 10 minutes 
(Notify the study team in advance if you have any allergies or intolerances to these 
foods). The eggs in this meal contain a small amount of radioactive material. This allows 
us to time the movement of food through your stomach by taking pictures (scans) through 
the use of an external camera.   
• At the completion of the breakfast test meal, you will be instructed to stand in front of a 
special camera and pictures will be taken at specific intervals. Each of these scans will 
take approximately 5 minutes. This entire test takes about 4 hours to complete.  Please do 
not eat or drink anything (except the meals provided and water) until after the 4 hour 
scan. 
 
This visit will last approximately 4 to 5 hours. 
 
Randomization and study medication dispensed: 
You will report to the CRTU, fasting is not required unless you are combining this visit with the 
Baseline Gastric Emptying test. 
 
 
 


 
 
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At this visit we will: 
• Measure your “vital signs” (blood pressure, temperature, heart and breathing rates) 
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must be negative) within 48 hours prior to study medication being dispensed.   
• Dispense a five-week supply of your study medication with instructions on how to 
stepwise increase the dose of medication in accordance with guidance from FDA, as 
detailed below. You will be randomized to the 20mg/kg of Cannabidiol treatment group 
or the placebo group (inactive). A placebo contains no active ingredient. Your chance of 
receiving the study medication is 50%, like the flip of a coin.  
• The starting dosage is 2.5 mg/kg twice daily (5 mg/kg/day). You will receive a Dosing 
Information sheet which shows the amount of study medication to ingest. 
• You will receive a separate form called Patient Medication Guide, which is information 
provided by the Food and Drug Administration to inform patients receiving the study 
medication of potential risks. 
• After one week, you will be contacted by phone by a member of the study team. If there 
are no side effects, the dosage may be increased to a maintenance dosage of 5 mg/kg 
twice daily (10 mg/kg/day).   
• After 2 weeks you will be contacted by phone by a member of the study team. If there are 
no side effects, the dosage will be increased to a 10mg/kg twice daily to a maximum of 
20mg/kg. 
• Equal amounts of placebo will be provided to correspond to the amounts shown for 
cannabidiol medication. 
• During the treatment, you will be asked to complete daily diaries that document your 
symptoms.  
 
End of Treatment Testing:  
You will have the following tests and procedures at the end of the 4th week of study treatment. 
The Gastric Volume and Nutrient Drink tests are combined on the same day. You will still be 
self-administering the medication daily on the morning of the test while you are still fasting. 
 
Take your study medication in the morning before you come in for the end of treatment 
testing. Do not eat anything for at least 8 hours before you attend the Clinical Research 
Unit for testing.  
• Note this time and provide this time to the nurse/study staff so they can document the 
time of your dosing that day.   
 
 
 


 
 
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Gastric Volume Test 
You will come to the CRTU after an 8 hour fast (nothing to eat or drink prior to your visit). 
Refrain from alcohol use for 48 hours prior to testing.  Refrain from caffeine (e.g. tea, coffee, 
energy drinks, and caffeine-containing sweets) for 24 hours before and until the end of testing.  
Note this test and the baseline buffet meal must occur on the same day.   
 
At this visit we will:  
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must prove negative) within 48 hours prior to this test.   
• Administer the Gastric Volume Test: This test involves SPECT imaging to measure the 
volume of your stomach with an external camera that revolves around the abdomen, 
while you are lying on a mattress and table. Stomach volume will be checked during 
fasting, starting 10 minutes after an intravenous injection of a radioactive material.  
• You will ingest 300 mL of a liquid nutrient drink (flavored Ensure) and one more image 
of the stomach will be obtained over the next 30 minutes. 
 
This visit will last approximately 1 hour.  
 
Nutrient Drink Test 
One hour after drinking Ensure for the Gastric Volume Test the Nutrient Drink test will start.  
 
At this visit we will:  
• Administer the Nutrient Drink Test: This test involves drinking Ensure at a rate of one 
ounce per minute until you cannot tolerate any more. At the same time, you will record 
your symptoms while you drink the Ensure and 30 minutes after you have reached the 
maximum volume you could bear.  
 
This visit will last approximately 60-90 minutes. 
 
Gastric Emptying Test 
• Same as Baseline Gastric Emptying Test, this visit will last approximately 4-5 hours.  
• Draw blood sample for end of one month treatment tests. This sample will study your 
serum transaminases (ALT and AST) and total bilirubin levels. 
• Collect the daily diaries that document your symptoms.  
• You will meet with a study physician to discuss any symptoms or changes to your health.  
 
The day following this visit, you will start the de-escalation plan described in your Dosing 
Information sheet. 
 


 
 
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End of Treatment Visit (optional) 
At this visit we ask that you return any unused medication so Mayo may properly dispose of the 
medication.  If this visit means that you will be traveling a good distance, we will give you a 
medication disposal bag with instructions during your last testing day on how to dispose of the 
remaining medication properly.  This medication should not be flushed down the toilet/sink or 
kept any longer than when you have completed the de-escalation of the medication as it expires 
at that time.  
 
This visit will last approximately 10-20 minutes. 
 
Tests done only for research purposes are not meant to provide clinical information or help care 
for you. The results are only important for research. Therefore, the results of tests done with your 
information and samples will not be provided to you. In the rare event that a finding might affect 
the health of you or your family, we will contact you and you can choose whether to receive or 
refuse the information. If you decide to follow up and further medical testing or care is needed, 
the costs will be billed to you or your insurance. 
 
 
What are the possible risks or discomforts from being in this research study? 
 
 
Most common side effects of Cannabidiol are as follows:  
• Rash 
• Diarrhea  
• Decrease in appetite 
• Sleep disturbance 
• Liver dysfunction including elevated liver enzymes, itching, jaundice (whites of eyes and 
skin turns yellow)  
• Somnolence  
• Fatigue 
• Increase risk of infections 
• Suicidal thoughts and behaviors 
• Risk of injury if operating heavy machinery 
 
If you develop any of these side effects, you are asked to contact a member of the study team as 
shown in contact information on page 3 of this consent form. 
 
 
 


 
 
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If you develop any clinical signs or symptoms suggestive of hepatic dysfunction (e.g., 
unexplained nausea, vomiting, right upper quadrant abdominal pain, fatigue, anorexia, or 
jaundice and/ or dark urine); a blood draw to test serum transaminases (ALT and AST) and total 
bilirubin levels will be performed.) 
 
As with any medication, allergic reactions are a possibility, including itching, rash, or difficulty 
breathing.  
 
There may be other risks of Cannabidiol that are currently unknown. 
 
Blood draw: The risks of drawing blood include pain, bruising, lightheadedness, and/or fainting, 
or rarely, infection at the site of the needle stick.   
 
Radiation: You will be exposed to radiation during the Gastric Emptying and the Gastric 
Volume tests in this research study. The amount of radiation you will receive has a low risk of 
harmful effects.  
 
Test Meals: Participation in this study requires the consumption of standardized test meals.  You 
should inform the study team if you have any food allergies or intolerances. 
 
Questionnaires: During this study, we will ask you to fill out questionnaires about emotional 
health and mood. Some questions you will be asked to answer in the study questionnaires may 
make you feel uncomfortable.  You may choose not to answer any questions that make you feel 
uncomfortable.  
 
Genetic Testing: This study involves testing your DNA, which is the genetic information you 
inherited from your parents (also known as genetic testing). You will not be notified of the 
genetic test results for it may take several years for an accurate interpretation of the results to be 
developed and they will not be put into your medical record. 
 
Pregnancy and Birth Control:  
Women of child-bearing-potential will be able to participate in this study if they have a negative 
pregnancy test and agree to use acceptable birth control (see below) since the risks to an unborn 
child are either unknown or potentially serious.   
• Surgical sterilization 
• Approved hormonal methods, such as birth control pills, patches, injections, vaginal ring, 
or implants 
 
 


 
 
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• Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, 
cream, or gel that kills sperm) 
• Intrauterine device (IUD) 
• Abstinence (no sex) 
 
There is not enough medical information to know what the risks might be to a breast-fed infant 
or to an unborn child carried by a woman who takes part in this study. Breast-feeding mothers 
must stop breast-feeding to take part in this study.  
 
As part of this study a pregnancy test is required for all women who are able to become pregnant. 
Urine pregnancy tests will be done (at the beginning and end of the study and throughout the 
study whenever you will be exposed to radiation and/or start your medication) on all women of 
child bearing potential. You will be told the results of the pregnancy test. If the pregnancy test is 
positive, you will not be able to take part in the study. If you are postmenopausal, it must be 
documented in your medical history. This will confirm your postmenopausal status and no urine 
pregnancy testing will be required of you. 
 
 
Are there reasons you might leave this research study early? 
 
 
We will tell you about any new information that may affect your willingness to stay in the 
research study. 
 
You may decide to stop at any time. You should tell the Principal Investigator if you decide to 
stop and you will be advised whether any additional tests may need to be done for your safety.  
 
In addition, the Principal Investigator or Mayo Clinic may stop you from taking part in this study 
at any time:  
• if it is in your best interest,  
• if you don’t follow the study procedures,  
• if the study is stopped.  
 
If you leave this research study early, or are withdrawn from the study, no more information 
about you will be collected; however, information already collected about you in the study may 
continue to be used.  
 
We will tell you about any new information that may affect your willingness to stay in the 
research study. 


 
 
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What if you are injured from your participation in this research study? 
 
 
Where to get help: 
If you think you have suffered a research-related injury, you should promptly notify the Principal 
Investigator listed in the Contact Information at the beginning of this form. Mayo Clinic will 
offer care for research-related injuries, including first aid, emergency treatment and follow-up 
care as needed. 
 
Who will pay for the treatment of research related injuries? 
Care for such research-related injuries will be billed in the ordinary manner, to you or your 
insurance. Treatment costs for research-related injuries not covered by your insurance will be 
paid by Mayo Clinic. 
 
 
What are the possible benefits from being in this research study? 
 
 
This study may not make your health better. Others who have gastroparesis or functional 
dyspepsia may benefit in the future from what we learn in this research study. 
 
 
What alternative do you have if you choose not to participate in this  
research study? 
 
 
This study is only being done to gather information. You may choose not to take part in this 
study. 
 
 
What tests or procedures will you need to pay for if you take part in this  
research study? 
 
 
You won’t need to pay for tests and procedures which are done just for this research study.  
 


 
 
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These tests and procedures are:  
• Vital signs  
• Physical exam  
• Questionnaires 
• Blood tests  
• Urine pregnancy tests 
• Height and Weight 
• Placebo/Study Medication 
• Gastric Emptying test 
• Nutrient Drink test 
• Height and Weight 
• Placebo/Study Medication 
• Gastric Emptying test 
• Nutrient Drink test 
• Gastric Volume test 
 
However, you and/or your insurance will need to pay for all other tests and procedures that you 
would have as part of your clinical care, including co-payments and deductibles.  
 
If you have billing or insurance questions call Patient Account Services at the telephone 
number provided in the Contact Information section of this form. 
 
 
Will you be paid for taking part in this research study? 
 
 
You will be paid $800 if you complete the whole study. If you don’t complete the study, we will 
pay you part of the money. You will be paid $200 for completing baseline tests and $200 for 
completing the Clinical Research Unit visit after 2 weeks of treatment. You will receive $200 for 
completion of 4 weeks of treatment and you will be paid $200 upon completion of the end of 
treatment testing. Payment for participation in research is considered taxable income and 
reportable to the Internal Revenue Service (IRS).  Accounts Payable at Mayo Clinic will be 
given your name, address and Social Security number in order to issue a check for your study 
participation.  If you receive research payments totaling $600 or more in a calendar year, a tax 
Form 1099 will be sent to you.  For Mayo Clinic employees, research payments are included in 
your paycheck with applicable taxes withheld and reported on your Form W2 after calendar 
year-end. 
 


 
 
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If you live more than 50 miles away, you are eligible for reimbursement of travel expenses 
including lodging, up to a total of $400. In order to receive reimbursement, you must provide a 
copy of the original receipts for those expenses.  
 
There is a very small chance that some commercial value may result from the use of your 
sample. This could include new products like a drug or a test to diagnose a disease. If that 
happens, you will not be offered a share in any profits. 
 
 
Will your information or samples be used for future research? 
 
 
Identifiable information such as your name, Mayo Clinic number, or date of birth may be 
removed from your information or samples collected in this study, allowing the information or 
samples to be used for future research or shared with other researchers without your additional 
informed consent. 
 
Unless you give your permission below, your information or samples collected for this study will 
not be used or shared for future research, even if the identifiable information such as your name, 
Mayo Clinic number or date of birth is removed. 
 
We would like to keep your information and samples for future research. You can still take part 
in this current study even if you don’t want your information or samples used for future research.  
Researchers at Mayo Clinic who aren’t involved with this study may ask to use your information 
and/or samples for future research. Researchers at other institutions may also ask for a part of 
your information and/or samples for future studies. Unless you indicate otherwise, the future 
research may be on any topic. No direct benefits to you are expected from the future research. 
Your information and/or samples will only be shared consistent with your consent, and with all 
applicable laws and regulations. 
 
If you approve release of your information and/or samples by checking ‘yes’ below, Mayo may 
send the information and/or samples to researchers who request them, but Mayo will not send 
your name, address, phone number, social security number, or any other identifying information 
with the information and/or samples. Your information and/or samples may be sent with a code, 
and only the researchers for this study at Mayo Clinic would be able to link the code to you. 
 
Some future studies may examine your DNA, the genetic information you inherited from your 
parents (genetic testing).  If there are findings which may be useful for your health care, the 
researchers may contact Mayo Clinic, so Mayo Clinic can give you the option of learning the 


 
 
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results. You would be given general information on the potential risks, benefits, and costs of 
choosing to learn about the findings. 
 
To support future research, de-identified genetic information may be placed in databases 
accessible by the internet. Some of the information may be available to anyone using the 
internet, and some will be released only to approved researchers. Combined study information 
(including genomic summary results) may be published, but the information will not identify 
you.  
 
Even though information traditionally used to identify you will not be shared, people may 
develop ways in the future to allow someone to link your genetic information back to you. For 
this reason, confidentiality cannot be guaranteed. It is also possible that reidentified information 
could be used in discriminating ways, and there could be additional unknown risks. We will 
make every effort to protect your confidentiality. 
 
Please read the following statements and mark your choices: 
 
1.  I permit my information and samples to be stored and used in future research of 
gastroparesis or functional dyspepsia at Mayo Clinic: 
 
  Yes 
  No  
Please initial here: ________Date: ________ 
 
2.  I permit my information and samples to be stored and used in future research at Mayo 
Clinic to learn about, prevent, or treat any other health problems: 
 
  Yes 
  No  
Please initial here: ________Date: ________ 
 
3.  I permit Mayo Clinic to give my information and samples to researchers at other 
institutions: 
 
  Yes 
  No  
Please initial here: ________Date: ________ 
 
You may withdraw your consent for future use of your information and/or samples at any 
time, by writing to the Principal Investigator at the address provided in the “Contact 
Information" section of this consent form. 
 
Your information and/or samples would be removed from any repository where they are stored, 
if possible. Information and/or samples already distributed for research use will not be retrieved.  
 
 
 


 
 
Approval Date:  
April 27, 2022 
Not to be used after: March 22, 2023 
 
 
IRB#: 19-002483 00 
Page 17 of 20 
IRB Doc. Ctrl # 10013.32 
 
 
 
 
 
 
 
Name and Clinic Number 
 
How will your privacy and the confidentiality of your records be protected? 
 
 
Mayo Clinic is committed to protecting the confidentiality of information obtained about you in 
connection with this research study. 
 
We will be storing research material in secure areas and password-protecting study data stored 
on computers.  
During this research, information about your health will be collected.  Under Federal law called 
the Privacy Rule, health information is private.  However, there are exceptions to this rule, and 
you should know who may be able to see, use and share your health information for research and 
why they may need to do so.  Information about you and your health cannot be used in this 
research study without your written permission.  If you sign this form, it will provide that 
permission (or “authorization”) to Mayo Clinic. 
 
Your health information may be collected about you from: 
• Past, present and future medical records. 
• Research procedures, including research office visits, tests, interviews and 
questionnaires. 
 
Your health information be used and/or given to others: 
• Do the research. 
• Report the results. 
• See if the research was conducted following the approved study plan, and applicable rules 
and regulations. 
 
Your health information may be used and shared with:  
• Mayo Clinic research staff involved in this study.  
• The Mayo Clinic Institutional Review Board that oversees the research.  
• Researchers involved in this study at other institutions. 
• Federal and State agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health and other United States 
agencies) or government agencies in other countries that oversee or review research. 
• The sponsor(s) of this study and the people or groups it hires to help perform this 
research. 
• A group that oversees the data (study information) and safety of this research. 
 
 
 


 
 
Approval Date:  
April 27, 2022 
Not to be used after: March 22, 2023 
 
 
IRB#: 19-002483 00 
Page 18 of 20 
IRB Doc. Ctrl # 10013.32 
 
 
 
 
 
 
 
Name and Clinic Number 
How your information may be shared with others: 
While taking part in this study, you will be assigned a code that is unique to you, but does not 
include information that directly identifies you. This code will be used if your study information 
is sent outside of Mayo Clinic. The groups or individuals who receive your coded information 
will use it only for the purposes described in this consent form. 
 
If the results of this study are made public (for example, through scientific meetings, reports or 
media) information that identifies you will not be used. 
 
In addition, individuals involved in study oversight and not employed by Mayo Clinic may be 
allowed to review your health information included in past, present, and future medical and/or 
research records. This review may be done on-site at Mayo Clinic or remotely (from an off-site 
location). These records contain information that directly identifies you. However, the 
individuals will not be allowed to record, print, or copy (using paper, digital, photographic or 
other methods), or remove your identifying information from Mayo Clinic. 
 
Is your health information protected after it has been shared with others? 
Mayo Clinic asks anyone who receives your health information from us to protect your privacy; 
however, once your information is shared outside Mayo Clinic, we cannot promise that it will 
remain private and it may no longer be protected by the Privacy Rule. 
 
 
Your Rights and Permissions 
 
 
Participation in this study is completely voluntary. You have the right not to participate at all.  
Even if you decide to be part of the study now, you may change your mind and stop at any time.  
You do not have to sign this form, but if you do not, you cannot take part in this research study. 
 
Deciding not to participate or choosing to leave the study will not result in any penalty.  Saying 
‘no’ will not harm your relationship with your own doctors or with Mayo Clinic. 
 
If you cancel your permission for Mayo Clinic to use or share your health information, your 
participation in this study will end and no more information about you will be collected; 
however, information already collected about you in the study may continue to be used. 
 
 
 


 
 
Approval Date:  
April 27, 2022 
Not to be used after: March 22, 2023 
 
 
IRB#: 19-002483 00 
Page 19 of 20 
IRB Doc. Ctrl # 10013.32 
 
 
 
 
 
 
 
Name and Clinic Number 
You can cancel your permission for Mayo Clinic to use or share your health information at any 
time by sending a letter to the address below: 
 
Mayo Clinic 
Office for Human Research Protection 
ATTN:  Notice of Revocation of Authorization 
201 Building 4-60 
200 1st Street SW 
Rochester, MN  55905 
 
Alternatively, you may cancel your permission by emailing the Mayo Clinic Research Subject 
Advocate at: researchsubjectadvocate@mayo.edu. 
 
Please be sure to include in your letter or email: 
• The name of the Principal Investigator, 
• The study IRB number and /or study name, and 
• Your contact information. 
 
Your permission for Mayo Clinic to use and share your health information lasts until the end of 
this study, unless you cancel it.  The study does not end until all data has been collected, checked 
(or audited), analyzed, and reported. Because research is an ongoing process, we cannot give you 
an exact date when the study will end. Sometimes this can be years after your study visits and/or 
activities have ended. 
 
 
 


 
 
Approval Date:  
April 27, 2022 
Not to be used after: March 22, 2023 
 
 
IRB#: 19-002483 00 
Page 20 of 20 
IRB Doc. Ctrl # 10013.32 
 
 
 
 
 
 
 
Name and Clinic Number 
 
Enrollment and Permission Signatures 
 
 
Your signature documents your permission to take part in this research.  
 
 
 
  
 
 
 
/        /  
 
 
   : 
       AM/PM   
Printed Name  
 
 
 
Date 
 
 
 
Time   
 
 
 
 
_______________________________ 
Signature 
 
 
 
Person Obtaining Consent  
• I have explained the research study to the participant. 
• I have answered all questions about this research study to the best of my ability. 
 
 
 
  
 
 
 
/        /  
 
 
   : 
       AM/PM   
Printed Name  
 
 
 
Date 
 
 
 
Time           
 
 
_______________________________ 
Signature