Evaluation of a Keto-Like Supplement on Brain Responses to Emotional Stimuli in Depression

Exploratory Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Effect of a Keto-Like Supplement in Depressed Patients on Functional Brain Responses to Positive and Negative Stimuli

This study aims to determine whether a keto-like supplement relative to placebo results in functional brain changes during fMRI tasks evaluating positive and negative valence in individuals with moderate to severe depression. In this double-blind randomized placebo-controlled trial, 75 individuals with a Patient Health Questionnaire (PHQ-9) scale score ≥ 10 (MDD) will be enrolled to participate in an 8-week treatment study to obtain 60 completers. Participants will be randomized with a 1-1 ratio to receive the keto-like supplement (n= 30 completers) or placebo (n=30 completers) taken orally three times per day for 8 weeks. Participants will undergo a 10.5-hour screening/baseline evaluation visit split over 2 days at week 0 including questionnaires, neuroimaging before and after supplement or placebo administration and blood draws, office visits at week 2 (1.5 hours), week 4 (3 hours), week 6 (0.5 hours), week 8 (6 hours), a follow-up visit at week 10 (1.5 hours) and two phone calls between visits (weeks 1 and 3) during which a brief clinical assessment will be obtained (10 minutes each). The total time involved in the study is approximately 23.5 hours.

Study Overview

• Status: Recruiting
• Conditions: Depression
• Intervention / Treatment: Dietary supplement: Keto-like supplement; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Teresa Victor, PhD; Phone Number: 918-502-5108; Email: tvictor@laureateinstitute.org
• Study Contact Backup: Name: Colleen McCallum; Phone Number: 918-502-5180; Email: cmccallum@laureateinstitute.org

Study Locations

• United States
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Recruiting
      • Laureate Institute for Brain Research
      • Contact: Teresa Victor, PhD; Phone Number: 918-502-5108; Email: tvictor@laureateinstitute.org
      • Contact: Colleen McCallum; Phone Number: 918-502-5180

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meets the Diagnostic and statistical manual - 5 (DSM-5) diagnostic criteria for MDD without psychotic features (past or present), as confirmed by the M.I.N.I v7.0
• PHQ-9 score of ≥10
• C-Reactive Protein (CRP) value > 1
• Age 18-65
• Consent ability and written consent
• Body Mass Index (BMI) between 19 and 38 kg/m2
• Medically stable based on clinical laboratory tests, medical history and vital signs
• No intention to become pregnant during the study
• A woman of childbearing potential must have a negative serum pregnancy test at screening
• Consent that possible random finding is reported (e.g. brain abnormality during imaging)

Exclusion Criteria:

• Has a current or recent history of clinically significant suicidality
• Has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 12 months before screening
• Has positive test result(s) for alcohol or drugs of abuse (including methadone, opiates, cocaine, cannabinoids, amphetamine/methamphetamine and ecstasy)
• Has a current diagnosis of a psychotic disorder (e.g. schizophrenia, bipolar disorder), an eating disorder (e.g. anorexia, bulimia), or learning disability or a personality disorder that is considered by the investigator to interfere with the ability of the subject to adhere to the protocol (e.g. narcissistic personality, borderline personality disorder)
• Change in medication dose and/or frequency within the last 6 weeks. Participants must be on stable medications for 6 weeks prior to enrollment.
• Plans to change medication dose/frequency during the course of the study. Must plan to remain on stable dose for the duration of the study, unless otherwise indicated by their provider during the course of the study.
• Plans to take vitamins and/or mineral supplements during the study. Must refrain for the duration of the study
• Unable to complete MRI scans
• Is a woman who is pregnant or breast feeding
• Plans to conceive a child while enrolled in this study or within 3 months after the last dose of the keto-like supplement
• Has received an investigational drug/vaccines, used an invasive investigational medical device within 60 days before the planned first dose of the keto-like supplement or has participated in 2 or more interventional clinical studies in the previous 1 year, or is currently enrolled in any drug or non-drug interventional study.
• Has had major surgery, (i.e. requiring general anesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time they are expected to participate in the study.
• Intake of Omega 3 fatty acids (DHA, EPA, fish oil supplements)
• Significant cognitive impairment, clinically relevant or progressive disease (e.g., liver, kidney, cardiovascular system, respiratory tract, vascular system, brain, metabolism, thyroid) that could affect the course of the study
• Known metabolic disorders (e.g., fatty acid oxidation disorders, ketolysis/ketogenesis or glucogenesis disorder, hyperinsulinism (e.g., pancreatic neuroendocrine tumor), pyruvate carboxylase deficiency, Type 1 and Type 2 diabetes
• Allergy to Stevia sweetener, malic acid or orange flavoring
• Concern for inability to maintain adherence to the keto-like supplement administration protocol
• Currently practicing a ketogenic or paleo diet or planning to do so during the study period.
• Change in body weight of more than 5 kg within one month before the start of the intervention
• Medical, psychiatric or other conditions that restrict the patient's following abilities: to interpret the study information, to give informed consent, to adhere to the rules of the protocol, or to complete the study
• Contraindications to MRI examinations [persons with metallic implants (e.g., intracranial metal clips) and carriers of electronic devices (e.g., pacemaker) or persons with claustrophobia]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Keto-like supplement; Participants will receive standardized 9.25g stick packs of the keto-like supplement. The study participants will take one of these stick packs dissolved in water three times a day (morning, noon, and evening) for 8 weeks.	Dietary supplement: Keto-like supplement; Participants will consume 9.25g stick packs of the keto-like supplement dissolved in water 3 times per day for 8 weeks.
Placebo Comparator: Placebo; Participants will receive standardized 9.25g stick packs of placebo. The study participants will take one of these stick packs dissolved in water three times a day (morning, noon, and evening) for 8 weeks.	Dietary supplement: Placebo; Participants will consume 9.25g stick packs of placebo dissolved in water 3 times per day for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD response during Monetary Incentive Delay Task	P5vP0 contrast in the nucleus accumbens during the Monetary Incentive Delay Task	week 0 pre, week 0 post, week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD response during Adjective Task	SELFvWORD contrast in the medial prefrontal cortex during the Adjective task	week 0 pre, week 0 post, week 8

Collaborators and Investigators

• Sponsor: Laureate Institute for Brain Research, Inc.
• Investigators: Principal Investigator: Martin Paulus, MD, Laureate Institute for Brain Research

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: February 8, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression
• Other Study ID Numbers: 2022-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No