A Cross-over Pilot Trial to Determine the Effect of an LSU Patented Dietary Herbal Supplement on Quality of Life
Phase: NA
Conditions: Quality of Life
Sponsor: Pennington Biomedical Research Center

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Protocol Title: A Cross-over Pilot Trial to Determine the Effect of an LSU Patented 
Dietary Herbal Supplement on Quality of Life
PI Name:
Frank Greenway, MD
Sub-Investigator’s Name(s): Prachi Singh, PhD
Protocol Version Date:
December 16, 2021
IRB Review History
Modification 3
Objectives
Specific Aim 1: Compare the quality of life using the validated Chubon Quality of Life 
Rating scale after taking the supplement or the placebo at baseline followed by a 2-
week washout, then 1 week taking the supplement or placebo that was not taken in the 
first period. 
Specific Aim 2: Compare the safety of the supplement by evaluating questionnaires, 
chemistry panel, CBC, Janus 3, adverse events and polysomnography at baseline and 
after 1 week of nightly administration with the supplement or the placebo before and 
after a 2-week washout.   
Hypothesis: The supplement will improve the quality of life compared to the placebo 
condition
Background
 Jack Losso and Jose Andino at Louisiana State University Agricultural Center 
developed a novel dietary herbal supplement consisting of at least two components 
chosen from the following six foods. 1. Collagen peptides of less than 3500 Daltons and 
preferably less than 2,000 Daltons derived from animals like cows, or other glycine-rich 
peptides. 2. Theanine, a component of decaffeinated green tea. 3. lactucopicrin, 
deoxylactucopicrin or another lactucopicrin derivative found in chicory.  4. Hyaluronic 
acid, a component of cartilage.  5. epigallocatechin gallate, a component decaffeinated 
green tea. and 6. quinic acid found in chicory.  This dietary supplement contains chicory 
and decaffeinated green tea containing epigallocatechin gallate. These ingredients are 
thought to decrease Janus kinase 3 (JAK-3) and people who have tried the supplement 
claim that it made them feel better, made them feel more alert and improved their 
quality of life.   
This trial is designed to measure the quality of life in response to taking the novel 
supplement.  People over 50 years of age with difficulty sleeping frequently feel tired 
and lack in energy which degrades their quality of life.  We will test the effect of the 
dietary herbal supplement on quality of life using a validated questionnaire in humans 
with difficulty sleeping over 50 years of age compared to a placebo in a crossover trial 
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comparing the supplement to a placebo after 1 week of administration separated by a 2-
week washout period.  
The dietary herbal supplement comes in a liquid that is dissolved in flavored water and 
administered orally in the evening in a 1.79 ounce portion an hour or two before 
bedtime.  Uncontrolled pilot data was generated in 12 people suffering from trouble 
sleeping who took the dietary herbal supplement for 1 week.  They awoke refreshed, felt 
more alert and felt that the quality of their lives had improved on the supplement.  This 
study will evaluate quality of life in a controlled crossover trial using a validated quality 
of life measure (1).  Since the participants in the pilot clinical trial all had trouble 
sleeping, we want to understand the safety of the supplement in people with sleep 
problems, and we also want to understand as much as possible the nature of the sleep 
difficulty and how the sleep difficulty is related to the stated improvement in quality of 
life.  The polysomnography is the test that allows the determination of the 
characteristics of the sleep difficulty and the questionnaires are also helpful in 
determining in what way the quality of life is improved, if the controlled trial confirms the 
findings of the pilot uncontrolled trial.   
Inclusion and Exclusion Criteria
Subjects will be recruited through the Pennington Recruiting Department
Subjects who meet the following criteria will be included in the study.
1. Healthy male or female subjects
2. 50 years of age or older
3. Willing to have blood stored for future research. 
4. Usual bedtime between 9 pm and mid-night
5. Chronic difficulty sleeping (trouble sleeping on average for more than 3 nights 
per week, meeting the International Classification of Sleep Difficulty (ICSD-2*) for 
at least 6 months.
6. Insomnia Severity Index score greater than or equal to 10 and a minimum of 30 
minutes of either sleep-onset latency (SL) or wake after sleep onset (WASO).
7. *ICSD-2 general criteria for sleep difficulty:
A. A complaint of difficulty initiating sleep, difficulty maintaining sleep, or waking 
up too early, or sleep that is chronically non-restorative or poor in quality.
B. The above sleep difficulty occurs despite adequate opportunity and 
circumstances for sleep.
C. At least one of the following forms of daytime impairment related to the 
nighttime sleep difficulty is reported by the patient:
a. Fatigue or malaise.
b. Attention, concentration, or memory impairment.
c. Social or vocational dysfunction or poor school performance.
d. Mood disturbance or irritability.
e. Daytime sleepiness.
f.
Motivation, energy, or initiative reduction.
g. Proneness for errors or accidents at work or while driving.
h. Tension, headaches, or gastrointestinal symptoms in response to sleep 
loss.
i.
Concerns or worries about sleep.
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Subjects that meet the following criteria will be excluded from the study
1. Have diabetes.
2. Are taking sedating or hypnotic medications.
3. Taking any chronic medication for which the dose has not been stable dose for 1 
month or longer.
4. Have a sleep disorder other than difficulty sleeping such as sleep apnea
5. Adults unable to consent
6. Individuals who are not yet adults (infants, children, teenagers)
7. Pregnant women
8. Prisoners
Number of Subjects
Ten subjects will be enrolled in this cross-over study consisting of a screening visit and 
four study visits
Recruitment Methods
The subjects will be recruited through the Pennington Advertising and Recruiting 
Departments and connections with Dr. Schwab who is a sleep specialist.
We anticipate a successful recruitment from a past history of referrals from Dr. Schwab
The advertisements will be developed by the marketing department and submitted for 
IRB review.  
Study Timelines
The duration of each subject’s participation will be approximately one month.  There will 
be a 1-week period of taking the supplement or the placebo, a 2-week washout and 
another 1-week period of consuming the placebo or supplement not taken in the first 
arm of the crossover trial  
The grant was issued in February of 2020 and should be completed within a year.  The 
Covid-19 problem has delayed the start of the study, but we hope to complete the study 
by the end of 2022.
We anticipate finishing the trial in 12 weeks, if we enroll a subject each week.  The 
primary analysis should be completed in the following 2 weeks and the report submitted 
to the Lift Grant Administration 4 weeks from the study completion.
Study Endpoints
Primary Endpoint: 
1. The Chubon Quality of Life Rating Scale. This scale has a test-retest stability of 
0.91, Chronbach’s alpha for variety of group ranges from 0.74 to 0.95 for internal 
consistency (2).  
Secondary Safety Endpoints:  
1. The Insomnia Severity Index questionnaire
2. The Epworth Sleepiness Scale questionnaire
3. The Pittsburgh Sleep Quality Index questionnaire
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4. Janus-3 kinase  
5. Polysomnography
6. 7-day accelerometry
7. Chemistry panel and CBC
8. Adverse events
 Procedures Involved
Subjects will have a screening visit and home oximetry to rule out sleep apnea. Sleep 
apnea is characterized by episodes in which people stop breathing during sleep. During 
this cessation of breathing the oxygen in the blood decreases and the lowered oxygen 
awakens the person.  A pulse oximeter is a device that measures the oxygen in the 
blood stream.  If the person experiences drops in blood oxygen during the night, it 
would be consistent with the person having sleep apnea.  If someone screened for the 
study has episodes of low blood oxygen as measured by the pulse oximeter, they will 
be referred to their primary physician or a sleep specialist to have a formal sleep study, 
using polysomnography.  That test can not only diagnose sleep apnea, but also define  
whether there is need for treatment of sleep apnea.  Sleep apnea is treated with 
Continuous Positive Airway Pressure (CPAP). Subjects meeting the inclusion and 
exclusion criteria will have questionnaires, blood testing and polysomnography and then 
start one week of a dietary herbal supplement or placebo.  The testing done on test day 
one will be repeated after 1 week.  After a 2-week washout period, the same procedures 
will be repeated at baseline that were performed on week-1.  The supplement or 
placebo not given in the first testing period will be given in the 1-week testing period.   
Schedule of Events
Week
Scr
Base 1
3
4
Consent
x
Medical Questionnaire
x
Vital signs
x
x
x
x
x
Height
x 
Weight
x
x
x
x
x
Polysomnography
x
x
x
x
Oximetry (R/O Sleep Apnea)
x
Chubon Quality of Life Rating
x
x
x
x
Insomnia Severity Index
x
x
x
x
x
Epworth Sleepiness Scale
x
x
x
x 
Pittsburgh Sleep Quality Index
x
x
x
x
Multidimensional fatigue Inventory
x
x
x
x
7-Day Actigraphy &Sleep Diary
X
x
x
Actigraphy During Sleep Test
x
x
x
x
Chemistry Panel, CBC
x
x
x
Janus kinase 3,
x
x 
Archive Serum and Buffy Coat
x
x
Adverse Events
x
x 
Dispense/collect Test material
x
x
x
x
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Screening visit:  Subjects will come to the screening visit having fasted for 10 hours 
except for water. Subjects will give informed consent, have vital signs height and weight 
measured, have blood drawn for a chemistry panel, CBC, complete a health 
questionnaire and complete the validated questionnaire, the Insomnia Severity Index.    
Subjects will have overnight oximetry to screen for sleep apnea rather than true difficulty 
sleeping.  Subjects will be asked to wear an actigraphy to measure motion/activity 
during the day and night for 7 days. Subjects will be asked to keep a sleep diary for 7 
days and return the diary, along with the actigraphy to the study staff for review. Those 
passing the screening visit will return for study visit one.
Study visit 1:  Subjects will come to the sleep lab at 7:00 pm after having eaten dinner 
at home for an overnight polysomnography test that includes oximetry and actigraphy. 
Subjects will be asked to sleep from 10:00 pm to 6:00 am the next day. The following 
morning subjects will complete 5 validated questionnaires: the Insomnia Severity Index, 
the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Chubon Quality 
of Life Rating Scale, and the Multi-dimensional Fatigue Inventory.  Unless a specific 
cause like sleep apnea is identified as the reason for the fatigue symptoms, the subjects 
will be given a week’s supply of the dietary supplement or placebo with instructions to 
take 2 ounces an hour before bedtime.  The study order of the supplement or placebo 
will be assigned randomly.  Subjects will be asked to use actigraphy and keep a sleep 
diary for the 7-day period until their next visit.
Study Visit 2: The subject will return in 1 week (±3 days) for a repeat polysomnography 
test, 1 hour before which the subject will take the assigned study supplement or 
placebo.  Upon awakening the next morning, the subjects will have a blood drawn for a 
chemistry panel, a CBC and Janus kinase 3.  Subjects will also have blood drawn to 
archive serum, buffy coat and EDTA plasma.  On awakening the next morning they will 
be asked to complete the 5 validated questionnaires: Insomnia Severity Index, the 
Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Chubon Quality of 
Life Rating Scale and the Multi-dimensional Fatigue Inventory. 
After a 2-week washout period subjects will return for visit 3.
Study visit 3: This visit occurs after a 2-week washout period, and is the same as visit 
1, only the supplement or placebo will be the one the subject was not assigned at study 
visit 1 (dietary supplement or placebo).
Study visit 4: This visit is the same as visit 2, and will be the end of the trial.
Blood testing: There is the possibility of infection and/or pain and bruising at the vein 
on the arm where the needle is inserted.  Aseptic (sterile) technique and trained 
personnel minimize these risks. 
Questionnaires: There are no known risks to completing the questionnaires
Measuring height, weight, blood pressure and pulse rate has no known risks
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Actigraphy is wearing a wrist watch-like device that measures motion.  Actigraphy has 
no known risks
Sleep Diary is to keep track of your sleep habits and experiences.  There are no known 
risks in keeping a sleep diary.
Oximetry is a device that is worn on the finger like a thimble and measures the oxygen 
in your blood using a light.  There are no known risks to wearing an oximetry device
Dietary Supplement is a mixture of 3 foods, a component of chicory, decafinated green 
tea powder and another component of green tea.  The supplement has no known risks.
Ingredients: each bottle contains a mixture of 5 grams of collagen peptides, 5 
grams of green tea extract, 1 gram of chicory extract, 7 grams of sweetener (half 
sugar and half erythritol), 0.2% potassium sorbate (as a preservative, 0.1% 
flavor, 60ml boiling water is added and colled to 185 degrees F.  53 ml or 1.79 
ounces is hot packed in a seal proof bottle that can be stored at room 
temperature or under refrigeration in this ready to serve format. 
Dose: The totla volume of each bottle is 53mL or 1.79 ounces and each bottle is 
one dose
Lot number:  The lot number is 2008-1for the supplement and 2008-2 for the 
placebo.  The supplement and placebo were prepared on August 17, 2020
Preparation: The supplement and the placebo were prepared at the LSU Food 
Incubator.  
Temperature: The supplement and placebo have been stored at room 
temperature.
Shelf-life: The shelf-life of the supplement is at least 2 years at room 
temperature.  The product was hot packed and contains potassium sorbate 
which is a preservative for long-term storage.  The expiration date for the 
supplement and placebo is August 17, 2022 and it is presently being stored in 
the Pennington pharmacy. The results of the stability study are attached.
Polysomnography (PSG) is an overnight video sleep study. PSG will include 
electroencephalography, electrooculography, electromyography, electrocardiography, 
pulse oximetry, nasal pressure transducer, oronasal thermocouple, calibrated 
respiratory inductance plethysmography. Sleep staging and events will be scored by 
registered PSG technologists according to established criteria.
Data and Specimen Banking
White blood cells called the buffy coat, serum from the blood  and EDTA plasma will be 
stored for future tests related to the effect of the supplement on the white blood cells or 
serum.  The white blood cells and serum will be frozen and used over a period of 
several months. Any extra material may be stored for future tests related to insomnia or 
the effect of the supplement on white blood cells or serum.  The testing of the cells will 
be limited to the effect of the supplement on white blood cells and serum.
Power analysis.
No controlled trials of the supplement exist to power this study. This is a pilot study. if it 
is statistically insignificant, it will provide the basis for powering a definitive clinical trial.
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Data and Specimen Management
The demographic data will be described using summary statistics.  The comparisons of 
the supplement and placebo will be analyzed using paired t-testing.  Data will be stored 
in the Pennington Data base that is controlled by the Research Computing Group and is 
password protected.  Subjects in the trial will be given an A number which allows them 
to remain unknown to those analyzing the data.  The data will be stored indefinitely as 
has all study data generated at Pennington.  Buffy coats and serum will be stored at 
Pennington.  The buffy coats and serum will be stored indefinitely and be used to 
analyze the effect of the supplement on white blood cell and serum related to sleep 
difficulty. Any data transfer will be done by the Pennington Research Computing Group. 
Provisions to Monitor the Data to Ensure the Safety of Subjects
This is a minimal risk study, but the investigators will keep in close communication with 
the study coordinator to insure the study is executed properly and that the study 
participants are not having any concerning side effects.   
Withdrawal of Subjects
Subjects will be withdrawn from the study should it be determined by the medical 
investigator that the potential benefits of the study are out-weighed by side effects.  
Subjects may also be withdrawn from the study if they are unwilling or unable to comply 
with the study requirements.
Risks to Subjects
The only foreseeable risks of this study are those associated with drawing blood.  There 
is the possibility of infection and/or pain and bruising at the vein on the arm where the 
needle is inserted.  Aseptic (sterile) technique and trained personnel minimize these 
risks.  The other procedures in this study have no known risks  
Potential Benefits to Subjects
The subjects in this study may experience an improvement in their quality of life in the 
week they take the supplement.  If that does occur, the effect is likely to go away after 
they are off the supplement for a day or two.  
Vulnerable Populations
This study excludes vulnerable populations
Multi-Site Research
This is a single site study.
Sharing of Results with Subjects
The study findings will be shared with the study participants.  We are expecting to 
present the study at a medical meeting and will share the abstract or press release with 
the study participants. The tests done in the study will be shared with the subjects and 
with their medical practitioner, if the patient wants that sharing to take place.
Setting
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The study will take place at the Pennington Center.  Pennington coordinators and other 
health professionals are well-trained to conduct the procedures in this clinical trial.  
Resources Available
We have done a study in which we recruited subjects with sleep difficulty.  We have 
also developed a good relationship with Kyle Schwab, a sleep specialist.  Between the 
patients with sleep problems wanting to enroll through information released by the 
Pennington Center and our relationship with the Sleep Center, we do not think that 
gathering study participants for the study will be difficult.  Pennington has all the 
resources needed for this study.
Prior Approvals
We have received approval from the LIFT program with funding to complete the study.
Compensation
Participants will receive $200 for completing the study. 
Confidentiality
The study data will be stored indefinitely at Pennington in the database and in the 
medical records area.  The data will be controlled by the Research Computing Group, 
and they will be responsible for any data transfer.  
Provisions to Protect the Privacy Interests of Subjects
The study subjects will be seen in private exam rooms to maintain their privacy.  The 
sleep studies will be done in a separate room with privacy curtains to for changing into 
bed clothing and getting redressed.  
Compensation for Research-Related Injury
No form of compensation for medical treatment or for other damages (i.e., lost wages, 
time lost from work, etc.) is available from the Pennington Biomedical Research Center.  
In the event of injury or medical illness resulting from the research procedures in which 
you participate, you will be referred to a treatment facility.  Medical treatment may be 
provided at your expense or at the expense of your health care insurer (e.g., Medicare, 
Medicaid, Blue Cross-Blue Shield, Dental Insurer, etc.) which may or may not provide 
coverage.  The Pennington Biomedical Research Center is a research facility and 
provides medical treatment only as part of research protocols.  Should you require 
ongoing medical treatments, they must be provided by community physicians and 
hospitals
Economic Burden to Subjects
None
Consent Process
The consent process will start with the potential subjects reading the consent form and 
one of the study team then going over it with them to be sure they understand it and to 
be sure all their questions are answered.  If subjects want to take the consent home and 
discuss it with their family or counselor, that will be allowed.  The consent will be 
discussed in a private examination room and the subjects will be encouraged to ask 
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questions throughout the study, even after the consent is signed with the study team 
emphasizing that giving consent is a process that continues throughout the trial.  
References
1. Chubon RA.  Development of a quality-of-life rating scale for use in health-care 
evaluaton.  Eval Health Prof.  1987;10(2):186-200.
2. Williams JI, Wood-Dauphinee SW.  Quality of life and technology assessment: 
monograph of the council on health care technology.  Institute of Medicine 
Council on Health Care Technology, Mosteller F and Falotico-Taylor J, Editors.  
Washington DC, National Academies Press (US) 1989.
Appendix A
Chubon Quality of Life Index
Appendix B
Insomnia Severity Index: 
https://www.ons.org/sites/default/files/InsomniaSeverityIndex_ISI.pdf 
Appendix C
Epworth Sleepiness Scale: 
https://epworthsleepinessscale.com/about-the-ess/ 
Appendix D
Pittsburgh Sleep Quality Index
https://www.psychiatry.pitt.edu/sites/default/files/inline-files/PSQI%20Article.pdf 
Appendix E
Multi-dimensional Fatigue Inventory
https://www.med.upenn.edu/cbti/assets/user-
content/documents/Multidimensional%20Fatigue%20Inventory%20(MFI).pdf
Pennington Biomedical IRB FWA 00006218
Approved December 23, 2021