Ketogenic Intervention in Depression
Phase: NA
Conditions: Depression, Ketosis
Sponsor: Ohio State University

 
 
 
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Ketogenic Intervention in 
Depression(KIND) 
 
The Ohio State University 
 
IRB Approval   December 01, 2022 
 
IRB# 2022H0271 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IRB Protocol 
 
 

 
 
 
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Ketogenic Intervention in Depression (KIND Study) 
IRB Protocol  
 
 
 
Primary Investigators: 
 
 
 
Jeff S. Volek, PhD, RD 
Professor, Department of Human Sciences 
The Ohio State University 
305 Annie & John Glenn Ave 
Columbus, OH 43210 
Office: 614-688-1701 | volek.1@osu.edu 
 
Ryan Patel, DO, FAPA 
Psychiatrist, Counseling and Consultation Services 
Adjunct Clinical Assistant Professor, Department of Psychiatry 
1800 Cannon Drive, Suite 1030 
Columbus, OH 43201 
Office: 614-292-5766 
 
 
 
 
Jennifer Cheavens, PhD 
Professor, Department of Psychology  
1835 Neil Avenue 
Columbus, OH 43210  
614-247-6733 
 
 
 
 
Scott Hayes, PhD 
Associate Professor, Department of Psychology  
1827 Neil Avenue 
Columbus, OH 43210 
614-292-3385 
 
 
 
 
 
 
 
 
 

 
 
 
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SUMMARY AND BACKGROUND  
 
Major depression is a burgeoning problem that affects over five percent of adults worldwide1 and 
is rapidly increasing in the United States.  From the second quarter of 2019 to June of 2020, the 
prevalence of symptoms of depression spiked from 6.5 to 24.3% , which was largely attributed to 
the COVID-19 pandemic2. Major depression and suicidal ideation have increased markedly in 
young adults, particularly within college campuses. In 2020, counselors at the Ohio State 
University (OSU) experienced a surge in the number of students with various mental health issues 
with anxiety and depressive disorders being the most common. The escalating prevalence of 
depression bubbling under the surface of the ongoing COVID-19 pandemic represents a unique 
challenge that requires new and creative solutions.  
 
Current psychotherapy interventions, such as Behavioral Activation, Cognitive Behavioral 
Therapy, and Interpersonal Psychotherapy are associated with clinically significant decreases in 
depression for approximately half of the people enrolled in these trials3. Further, depression is 
often treated with medications such as selective serotonin reuptake inhibitors and tricyclic 
antidepressants. However, these drugs are associated with side effects such as anxiety, decreased 
libido, nausea, and insomnia which may exacerbate the same depressive symptoms they are 
intended to treat4.  
 
Poor metabolic health significantly increases risk of depression. For example, people with obesity 
are more likely to meet criteria for depression and report symptoms of depression5. Thus, 
additional co-therapies6, specifically those that might enhance current psychotherapy such as diet 
interventions7, are warranted in the treatment of major depressive disorder. Further, examining 
nutritional interventions may be particularly important following the onset of the COVID 
pandemic, given restrictions on activities and increased isolation. Most nutrition studies examining 
effects on depression have focused on single nutrients (e.g., omega 3 fatty acids, B-vitamins, 
tryptophan, specific minerals) with mixed results8. A more consistent improvement in depressive 
symptoms may be achieved by improving eating patterns, such has been shown with a 
Mediterranean diet9,10.  
 
Another eating pattern shown to have consistent benefits in metabolic health is a ketogenic diet 
(KD). KD interventions have demonstrated therapeutic effects in obesity, metabolic syndrome, 
and type 2 diabetes11-15. It was recently demonstrated that a group of military-affiliated students at 
OSU prescribed a KD were uniformly able to adhere to the diet for 12-weeks as demonstrated by 
average ketone >1 mM. They exhibited highly significant improvements in body composition, loss 
of visceral fat, and improvement in a host of metabolic markers16-18. In addition to global 
improvements in body composition and metabolic health, KDs may target neurochemicals, such 
as brain derived neurotropic factors (BDNF)19, and inflammation which may influence depression 
and cognitive functioning over time. For example, KDs may also have neuroprotective effects in 
the hippocampus, an important neural area cognitive function and mental health20,21. Recently, a 
KD was administered to adults who had been admitted to a psychiatric hospital and were suffering 
from various mental disorders. The dietary intervention lasted between 16 and 248 days and 
showed significant improvements in depression and psychotic symptoms22. Ketogenic diet 
interventions (and ingestion of ketone esters) have also been associated with more stable brain 
networks, assess with functional Magnetic Resonance Imaging (fMRI). Additionally, a novel but 
as yet under-appreciated effect of nutritional ketosis is to induce a broad-spectrum reduction in 

 
 
 
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inflammation in metabolically-impaired individuals12,14,23,24. Elevations in a range of inflammation 
biomarkers has been associated with severity of depression25,26.  
Although KDs have been proposed as a treatment option for mental health disorders, including 
schizophrenia23 and depression7, few human clinical trials have tested the efficacy of this eating 
pattern specifically in a population of adults with major depression. In patients with type 2 diabetes 
(n=262) prescribed a KD using a novel virtual care model (Virta Health), we observed significant 
improvements in depressive symptoms after 10-weeks, which were directly correlated with the 
degree of carbohydrate restriction and nutritional ketosis as assessed by blood concentrations of 
ketones27,28.  
 
IMPACT   
 
The overarching goal is to perform a pilot study to: (1) demonstrate that a well-formulated KD can 
be implemented in a university counseling treatment program for major depression, and  (2) test 
whether such a program results in reductions of symptoms of depression. We plan to recruit 60 
students with major depression who will receive coaching and support on a KD over a 12-week 
period; this will demonstrate initial feasibility of the diet. We hypothesize that participants will 
demonstrate improvements in metabolic health, mental health, cognition, and brain function (using 
Magnetic Resonance Imaging; MRI)29. The data from this pilot study will be used to generate 
effect size estimates to inform the design of an intervention study to compare efficacy of a KD to 
standard diet and/or other diet treatment strategies. The results from this open-trial will also be 
valuable for providing safety information and providing relevant mechanistic information 
regarding KD-induced improvements in depression.  
 
RESEARCH STRATEGY  
 
This will be a single arm prospective trial assessing feasibility of implementing a KD in up to 60 
participants with depression over 12-weeks. Participants who are MRI eligible will also have the 
option to complete pre- and post-intervention brain MRI. After enrollment, participants will 
complete a battery of baseline tests. The intervention will last 12-weeks with the primary efficacy 
outcomes assessed bi-weekly and other secondary/exploratory outcomes assessed at time points 
detailed in Table 1. Participants will receive standard of care clinical treatment for depression 
through the OSU Counseling and Consultation Services (CCS) throughout the intervention.  
 
OUTCOMES 
 
Primary Outcomes. Adherence will be determined by the number of participants completing the 
12-week intervention. We expect >80% of enrolled participants to complete the 12-week trial. 
Additionally, we will determine the number of participants who consistently maintain a level of 
nutritional ketosis (average ketones ≥0.5 mM).  
 
The primary efficacy outcome will be depression score as assessed by PHQ-9 and HRSD. The 
self-reported PHQ-9 is a measure of depression symptom severity. It maps onto DSM-5 criteria 
for Major Depressive Disorder and is widely used in both clinical and nutrition research settings. 
The HRSD is an observer-rated measure of depression mostly used in research settings; the HRSD 
will be used to provide objective and standardized ratings of symptom severity, including ratings 

 
 
 
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that require external observation such as psychomotor retardation. The PHQ-9 and HRSD will be 
administered bi-weekly to provide a trajectory of depression symptoms.  
 
Secondary Outcomes. In addition to changes in symptoms of depression, we will assess changes 
in a number of metabolic markers and cognitive markers of psychological health. We will assess 
the following to quantify these changes: Body weight, body composition, blood pressure, glucose, 
insulin, HbA1c, chemistry panel, lipids, and cognitive measures, structural and functional brain 
MRI).  To examine changes in inflammation, we will assess the following markers: interleukin 1, 
interleukin 6, C-reactive protein, tumor necrosis factor-alpha, and WBC count with differential.  
 
PARTICIPANTS 
We expect to enroll up to 60 young adults with major depression into a KD intervention over a 12-
week period. Participants will be  able to pick up study fliers or will be handed fliers by CCS team 
members.  Study fliers will include all inclusion and exclusion criteria and will provide potential 
participants with research team contact information. Participants must meet all inclusion criteria 
and none of the exclusion criteria as indicated on a prescreening checklist before baseline testing. 
Pre-screening and BL inclusion/exclusion criteria is outlined below. 
Inclusion Criteria:  
• OSU students (age 18-30 years at the time of enrollment) with confirmed major depressive 
disorder as determined by SCID-5 diagnosis at baseline testing.  
• Currently engaged in counseling treatment for depression at CCS  
• Available for a 12-week period and indicate willingness and ability to eat KD foods as 
prescribed 
Exclusion Criteria:  
• Disordered eating, as evidenced by meeting criteria for Anorexia Nervosa, Bulimia 
Nervosa, Binge Eating Disorder, Other Specified Eating Disorder, Unspecified Eating 
Disorder, or Avoidant Restrictive Eating Disorder during the SCID-5 interview at baseline 
testing.  
• Substantial imminent risk of suicide as assessed during the SCID-5 interview. 
• Body mass index (BMI) < 20 kg/m2 
• Habitual consumption of a structured low-carbohydrate diet in the last 6-months 
• Gastrointestinal disorders or allergies that would prevent adherence to prescribed diets 
• Alcohol consumption in excess of 3 drinks/daily or 14 drinks/weekly 
• Diagnosed diabetes, liver, kidney, or other metabolic or endocrine dysfunction, or use of 
diabetic medications other than metformin 
• Inability to access or prepare appropriate KD foods/meals  
• Pregnant, lactating, or planning on becoming pregnant during the study 
• Unwilling to perform finger-stick blood testing or continuous glucose/ketone monitoring 
Exclusion for optional MRI: 
• The CCBBI screening form (https://redcap.osumc.edu/redcap/surveys/?s=N3XJ4WC7T9) 
will be used to assess MRI eligibility. Endorsement of items that contraindicate MRI will 
serve as exclusion criteria (pacemaker, stint, claustrophobia, etc.).  
Recruitment: 
OSU students will be recruited through the Office of Student Life’s CCS, and through the 
recommendations of the 50+ counselors associated with the Health and Wellness Center who are 

 
 
 
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charged with the care and wellbeing of OSU students experiencing major depressive symptoms. 
All potential participants must be currently enrolled with the Student Life’s CCS. Initial screenings 
for qualifying inclusion and exclusion criteria will be conducted by Dr. Patel and his team. We 
expect to enroll between 30 and 60 participants. The total number of students who received clinical 
services through CCS during the 2020-2021 academic year was 5,488. Thus, recruiting 30 – 60 
participants who meet inclusion and exclusion criteria is an achievable goal.  
 
METHODS  
 
Study overview:  
 
 
Fig. 1 Experimental Approach.  
 Created with BioRender.com 
 
 
 

 
 
 
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Study Procedures 
The timeline of various study procedures is detailed in Table 1. 
 
Table 1: Study Assessment Timeline 
 
1.     SCID-5 RV: Structured Clinical Interviews will be used at baseline after Informed Consent to determine 
if participants are eligible to continue with the study’s dietary intervention. 
 
2.    WHO-5: The WHO-5 is a short 5 item questionnaire that will be used bi-weekly to assess participants 
psychological well-being.  This questionnaire will be administered digitally via RedCap or Qualtrics.   
3.     PHQ-9: The Patient Health Questionnaire-9 will be used bi-weekly to assess each participant’s degree 
of depression (i.e., intensity and severity).  This questionnaire will be administered digitally via RedCap or 
Qualtrics. 
4.    Depression Scale: The Hamilton Rating Scale for Depression is a questionnaire that will be given to 
participants and BL, week-6 and -12 of the intervention to evaluate improvements in depression symptoms. 
5.    CGM/CKM: Continuous Glucose/Ketone Monitors will be applied after Informed Consent. The sensor will 
be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~6- 
week intervals during the study. The sensor will be removed at the end of the final test day 
6.    Finger Stick BHB: Finger sticks will be taken daily in the morning, by the participant to determine ketone 
and glucose levels at a fasted state. Measurements will be reported daily in RedCap or Qualtrics. 
7.   Surveys/ Side Effects: Participants will complete the Automated Self-administered 24-hour Dietary 
Assessment Tool (ASA24®) at baseline.  They will also complete behavioral and cognitive surveys during 
each testing day. 
8.   Venous Blood Draw: A fasting blood draw will be taken from the antecubital vein during each testing day. 
9.   Body Composition: Anthropometric data will include: Lean Body Mass by DXA, BMI, height and weight. 
10.    Blood Pressure: This will be determined by manual cuff and recorded by research staff. 
Participants will wear a Bluetooth heart rate monitor chest strap throughout the test day. 

 
 
 
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11.   Cognitive Testing: Cognitive tests will be conducted via iPad to provide measures of global cognition 
and specific cognitive domains. 
12.    MRI: Structural and Functional MR imagining will be done to assess changes in cortical thickness, brain 
volume, and functional connectivity. 
Pre-Study Screening: Students with depression who are currently engaged with counseling 
treatment provided through the CCS, will be made aware of the study during their therapy sessions. 
Potential participants will be provided with a research flier by their CCS therapist. If the potential 
participant takes interest in the study, they will complete a pre-screening checklist which includes 
a brief summary of the study and a series of inclusion/exclusion criteria to which they will answer 
‘yes’ or ‘no’. If the potential participant passes this pre-screening checklist, they will be scheduled 
to meet with study staff for an informed consent meeting to thoroughly discuss the study, review 
informed consent and HIPPA information. Upon consent, the participant will then meet with study 
team for eligibility determination. 
 
Informed Consent and Eligibility Determination. Participants will review the informed consent 
and HIPAA information with study personnel. After providing consent, participants will complete 
clinical interviews and questionnaires, which may involve inquiry about personal information, 
including demographics, medical history, health behaviors, and current medications. These 
questions will ensure inclusion eligibility. Participants who meet eligibility criteria will be fitted 
with a Continuous Glucose and Ketone Monitor (CGM/CKM) and scheduled for their dietary and 
cognitive assessment appointment. MRI scanning will be an option for participants who are 
interested and eligible for MRI. Those interested in participating in the MRI sessions will complete 
the CCBBI MRI eligibility screening form and scheduled for MR imaging with study team. The 
schedule of study testing visits is shown in Table 2. 
 
Table 2: Scheduled Study Visits  
Week 
Appointment 
# 
Description 
Expected Time Frame 
Baseline 
1 
Determine potential participant interest in the 
study and go over pre-study eligibility form with 
CCS team member. A pamphlet describing the 
dietary protocol will be handed out at this time. 
1 hr 
Baseline 
2a 
Informed Consent Form & Structured Clinical 
Interview 
90 min 
If participant is ineligible or no longer interested, they are compensated, and 
study participation is terminated. 
If eligible and interested, participant continues in study as below: 
  
Baseline 
2b 
Mental Health Battery and Continuous Glucose 
Monitor / Continuous Ketone Monitor application 
90 min 
Baseline 
3a 
Weight, Hydration Status, Body Composition 
Testing, Survey/Side Effects, Venous Blood 
Draw, Body Composition, and Blood Pressure. 
1 hr 
Baseline 
3b 
Cognitive testing 
1 hr 
Baseline 
3c 
Dietary consult 
45 min 
Baseline 
3d* 
MR Testing 
1 hr 

 
 
 
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5 
4 
Continuous Glucose Monitor / Continuous 
Ketone Monitor application  
5 min 
6 
5 
Weight, Hydration Status, Body Composition 
Testing, Survey/Side Effects, Venous Blood 
Draw, and Blood Pressure. 
  
1hr 
 11 
6 
Continuous Glucose Monitor / Continuous 
Ketone Monitor application  
5 min 
 12 
7a 
Cognitive Tests  
1 hr 
12 
7b 
Weight, Hydration Status, Body Composition 
Testing, Survey/Side Effects, Venous Blood 
Draw, and Blood Pressure. 
1 hr 
12 
7c* 
MR Testing 
1 hr 
 
Testing Visits. As detailed in Tables 1 and 2, PHQ-9 data will be collected at baseline and bi-
weekly by means of an internet-based survey and questionnaire administration program (REDCap 
/ Qualtrics). HRSD data will be collected in-person or virtually by study assessors at baseline, 6- 
and 12-weeks. As part of their standard counseling protocol, counselors will also administer the 
CCAPS-34 to assess global mental health at baseline and 3-wk intervals. Other outcomes will be 
assessed at baseline, 6- and 12-weeks at a single visit in the PAES Building centrally located on 
the OSU campus (see Fig 1).  
 
For testing at the PAES (Fig 2), subjects will arrive to the lab in the morning after an overnight 
fast. We will test for hydration, measure height and body mass, and then have participants complete 
surveys followed by resting blood pressure. A phlebotomist will obtain blood samples from a 
forearm vein in subjects after sitting for 10-min. Appropriate sample tubes will be used for EDTA, 
sodium heparin, or serum for different analytes. A serum tube will be sent to Quest Diagnostics to 
assess standard chemistry panel (liver enzymes, kidney function, lipids, etc.).  
 
Serum and plasma will be immediately centrifuged and aliquoted into tubes and stored at -80°C 
until subsequent analyses. Samples will be thawed only once for analysis and assayed in duplicate 
for ketones, glucose, and insulin, which will be used to calculate an index of insulin resistance, 
and HbA1c. Extra serum and plasma will be archived for future analysis of biomarkers that may 
provide insight into novel associations with depression. We will determine body composition from 
a single whole-body scan using dual-energy x-ray absorptiometry (iDXA, Lunar Corporation, 
Madison, WI). Finally, subjects will complete a battery of computerized cognitive tests. Total time 
for this visit will be less than 2-hours.   
 

 
 
 
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Fig. 2 test day timeline. Created with BioRender.com 
 
Neurocognitive test materials and procedure. Testing sessions will be administered by trained lab 
staff. All participants will complete an assessment of cognitive function with the NIH Toolbox 
(IPAD-based assessments that examines cognitive function) and standardized neuropsychological 
testing (such as sub-tests from the Delis-Kaplan Executive Function System, Stroop Color Word 
Test, and Wechsler Memory Scale). Computer-based testing of memory (pictures and words) and 
executive function (attending to visually presented stimuli, such as scenes) may also be 
administered.  
 
The gradCPT contains grayscale photographs of mountain scenes and city scenes. Scene images 
gradually transition from one image to the next 31,32;). Participants are instructed to press the 
space bar on the keyboard for each city scene, and to withhold responses for mountain scenes. 
Practice trials will be given prior to the start of the task with feedback for each trial response to 
ensure that the task instructions were understood. The actual task lasts approximately 4 minutes 
and feedback is not provided during the task.  
 
 
A. 
Illustration of gradCPT. Scenes gradually 
transition from one image to the next image. 
Participants are instructed to respond to city 
scenes and withhold for mountain scenes 
(Esterman et al., 2012). 
 
 
 
 
MRI Image Acquisition (approximately 60 min). Participants who are MRI-eligible may volunteer 
for pre- and post-intervention MRI. We have the resources to complete pre- and post- intervention 

 
 
 
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MRI on approximately 15 volunteers, possibly more depending on availability of funding. Images 
will be collected on a 3T Siemens Prisma scanner at the Center for Cognitive and Behavioral Brain 
Imaging (CCBBI) located in the OSU Psychology building (1835 Neil Ave.). A contrast agent will 
not be used. Participants will enter the scanner room, lay supine on the MRI table, will be fitted 
with ear plugs (noise reduction), and will have their heads stabilized with cushions (to reduce head 
motion). The participants will be moved into the bore of the scanner, and localizer, structural, 
resting- and task-related functional images will be collected. Subjects will be screened for 
contraindications to MRI using the CCBBI screening form (i.e., for metal implants and other 
magnetic material that will interfere will MRI).  
 
To optimize semi-automated tissue and neuroanatomical classification, a whole-brain T1-weighted 
sequence and a T2-weighted sequence will be acquired. Cortical reconstruction and volumetric 
segmentation will be performed, and these data will be used to optimize registration and 
normalization of functional brain volumes.  
 
Resting-state fMRI: Whole brain echo-planar imaging (EPI) volumes sensitive to the BOLD signal 
will be acquired. Images will be re-aligned, un-warped, and normalized. Confounding effects of 
white matter, CSF signal, and head motion will be regressed from the functional time series, 
followed by bandpass filtering, linear detrending and smoothing, and whole brain resting state 
networks will be identified (e.g., default mode network, salience network, etc). 
 
Task-fMRI: During whole brain EPI data acquisition, participants will be presented with words 
and pictures and asked to make judgements about the stimuli, such as indicating whether a 
particular stimulus (e.g., face-name association, word, number, or letter) has been previously 
presented, if a presented stimulus is a city or mountain scene, the direction an arrow is pointing 
(left or right), if a pair of stimuli match (e.g., faces with neutral or emotional expressions; word 
with a face). Behavioral responses will be recorded with an MRI compatible button box.  
 
DIETARY INTERVENTION 
The diet intervention will start after all baseline testing is complete. Participants will receive 
extensive education and ongoing support from the dietetic team to achieve the nutritional goals of 
a well-formulated KD. Each participant may require slightly different levels of coaching 
depending on their baseline knowledge and individual situation. Thus, the intensity of engagement 
may vary across participants. We plan to provide a portion of their caloric intake in the form of 
staple food items in order to offset participant food costs, ensure nutrient quality, and facilitate 
adherence.  
The KD will follow general principles as we have described30 with the aim to achieve blood 
ketones >0.5 mM, which will require most participants to consume <50 g/day carbohydrate and 
~1.5 g/kg reference weight protein. Fat will comprise the remaining calories with an emphasis on 
monounsaturated and saturated sources from whole foods. A wide range of foods will be 
incorporated including non-starchy vegetables, fruits (berries, olives, tomatoes, lemons/limes), 
meats (beef, chicken, pork, fish, lamb), nuts and seeds, oils (olive, canola, coconut), cheese, butter, 

 
 
 
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cream, eggs, and fatty fish (salmon, sardines). Nutritional ketosis is associated with natriuresis that 
will lead to sodium and fluid loss if the extra sodium excreted is not compensated by individualized 
intakes. If untreated, the resultant hypovolemia can manifest in side effects and adrenal stress 
(often mis-characterized as ‘keto-flu’) that disrupts body fluid, electrolyte, and mineral status. 
Thus, slightly higher sodium and potassium intakes are required to offset the natriuresis, which 
will be achieved through the provision of broth/LMNT electrolyte packs and appropriate food 
sources and cooking methods. In addition, neuro-muscular irritability characterized by muscle 
cramping will be addressed with individualized supplementation with oral magnesium and 
calcium. Shelf stable items such as high-quality fats/salad dressings, salmon & sardine packets, 
jerky, cheese whisps, nuts and seeds, will be included in the starter and replenishing kits. 
 
DATA ANALYSIS AND STATISTICAL METHODS 
Patient demographic and characteristics information, pre- and post-intervention depression scores 
and other outcomes will be summarized for the KD group at every time point. Considering this is 
a pilot feasibility study, we will focus on calculating effect sizes. Changes in depression scores 
within the KD group will also be evaluated using a linear mixed model for repeated measures, with 
the baseline score potentially included as a covariate to control for baseline variability. The linear 
mixed models (Multi-level Model, MLM) will allow us to easily handle missing data (assuming 
Missing-at-random) and estimate within group effects from the same model. These models can 
also easily handle co-variates and are robust to violations of normality. Normality and 
heteroscedasticity will be checked using residual plots. All data that are non-normal may be either 
suitably transformed (e.g., log, Box-Cox) or analyzed using non-parametric methods (Kruskal-
Wallis test).  
 
Incidental Findings 
There may be incidental findings observed on MRI, cognitive, and fitness assessments. For each 
type of assessment, the participant’s primary care physician will be contacted within 30 days of 
incidental finding detection. Each participant will provide contact information for their healthcare 
provider at entry of the study. 
 
 
 
 
STUDY MONITOTRING 
Concomitant Medication/Supplements and Treatment 
All concomitant medications/supplements used 1 month prior to Screening Visit and during the 
study will be reported to the study personnel for assessment and recorded in the participant’s study 
documents.  
 
CONDUCT OF THE STUDY 
1. Ethics and Regulatory Considerations  

 
 
 
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This study will be conducted according to Good Clinical Practice Guidelines, the Declaration of 
Helsinki (2004) and United State Code of Federal Regulation Title 21. Signed written informed 
consent for participation in the study will be obtained from all participants before protocol-specific 
procedures are carried out. Participants will be informed of their right to withdraw from the study 
at any time. Participants will be informed that their participation in the study is completely 
voluntary, personal information will be both de-identified to preserve anonymity.  
 
2. Institutional Review Board  
The Investigator will ensure that an appropriately constituted IRB, in compliance with the 
requirements of 21 CFR 56, reviews and approves the clinical study. Before the study is started, 
the Investigator will forward copies of the protocol and consent form for this study to the IRB for 
review and approval. IRB approval must refer to the study by exact protocol title and number, 
identify the documents reviewed, and state the date of review. The IRB must be informed of all 
subsequent protocol amendments. No alterations, modifications to IRB-approved documents, 
including the protocol, protocol summary, consent form, recruitment materials and questionnaires 
will be allowed. The IRB must also be informed of all SAEs and of unexpected AEs as outlined in 
the IRB’s SOPs (standard operating procedures) or reporting guidelines.  
 
3. Informed Consent and Protected Health Information  
The study will be explained verbally as well as on the informed consent document. Each participant 
will be given ample opportunity to inquire about details of the study and to read and understand 
the consent form before signing it. It will be made clear that participants can withdraw from the 
study at any time.  
 
Each participant’s signed informed consent document must be kept on file by the Investigator. The 
participant should receive a copy of the informed consent document. A participant may not be 
admitted to the study unless informed consent of the participant (or his/her legally authorized 
representative) has been obtained.  
 
4. Participant Confidentiality  
The Investigator is responsible for ensuring that participants’ anonymity will be maintained. For 
all the data collected over the course of the study for each participant (i.e., records, biological 
samples and questionnaires) a unique subject identifier (i.e., a code) will be assigned and used 
instead of the subject’s name. The code for each participant which links the subject name with 
their identifier will only be available to research personnel. Electronic CRFs or other documents 
will identify participants by initials, number, or code, and not by name. The Investigator will keep 
a separate log showing codes, names, and addresses. Any records that contain the subject’s name 
and identifier will either be stored in the Clinical Psychology file storage room in a file cabinet 
(locked) or protected on a computer via password protection on the individual digital file and 
password protection on the computer the file(s) are stored on. All other records that contain the 

 
 
 
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subject identifier only will also be kept in either a file cabinet in our locked file storage room or 
on a password protected computer. Biological samples collected from each participant will be kept 
in a storage freezer labelled only with the subject identifier.  Subject names will never be used in 
any presentation or publication resulting from this study. The records will be maintained until the 
data are published and up to a maximum of ten years after the completion of the study. All records 
or biological data obtained after signing of the informed consent (including the screening visit, 
even for subjects that are not eligible for participation in the study) are treated with the same 
confidentiality safety measures as those subjects who qualify. Any information obtained during 
the prescreening for participants that were not eligible will be deleted. Any potential incidental 
findings from MRI, blood biomarkers, etc. will be shared with the participant. Incidental findings 
from the MRI imaging will be reported to the participants primary care physician within 30 days 
of finding. The remaining information (ie. Blood biomarkers) is non-diagnostic and will be 
provided so the participant may choose to share with their physician. 
 
5. Withdrawal of Participants from the Study  
Participants may be removed from the study for any of the following reasons:  
• 
A participant requests discontinuation;  
• 
The Investigator initiates removal for medical or compliance reasons;  
• 
Occurrence of any AE or condition that could, in the Investigator’s opinion, interfere with 
the evaluation of the effect of the study beverage or put the participant at undue risk.  
 
It is understood by all concerned that an excessive rate of withdrawals can render the study 
uninterpretable, therefore, unnecessary withdrawal of participants should be avoided. Should a 
participant decide to withdraw, all efforts will be made to complete and report observations as 
thoroughly as possible. In the event that a participant is withdrawn from the study, the reason for 
the withdrawal will be documented.  
 
 

 
 
 
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