Investigating the Evolutionary Impact of Metabolic Flexibility on Physical Activity-Dependent BDNF and Cognition: Insights From the Val66Met Polymorphism

NCT07218497 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: APP-24-05903
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if a state of ketosis and physical activity will increase serum BDNF concentrations and improve cognition, specifically in individuals who possess the Met allele from the BDNF Val66Met SNP. The main questions it aims to answer are:

• Does the combination of ketosis and physical activity increase serum BDNF concentrations and cognition?
• Do Met Carriers of the BDNF Val66Met SNP demonstrate a significantly larger change in serum BDNF after physical activity and a state of ketosis compared to Val/Val Homozygotes?
• Do Met Carriers of the BDNF Val66Met SNP demonstrate a significantly larger increase in cognition after physical activity and a state of ketosis compared to Val/Val Homozygotes? Researchers will compare a ketosis supplement to a placebo (a look-alike substance that contains no drug) to see if the ketosis supplement and physical activity increases serum BDNF and improves cognition. Participants will:
• Participate in a drug trial where they will be given the ketosis supplement, and a placebo trial where they will ingest a placebo.
• Participants will donate a whole blood sample and take a cognitive test before and after the ketosis and placebo trial.
• Participants will take a 30-minute treadmill test during both the ketosis and placebo trial, after ingesting either the drug or placebo for each respective trial.

Conditions

Cognition; BDNF

Keywords

Cognition; BDNF; Val66Met SNP; Physical Activity; Ketosis

Outcome Measures

Primary Outcomes (1)

• Serum BDNF

  Whole blood will be taken from participants before and after the treadmill test for both placebo and ketosis trial days. Serum will be extracted and an ELIZA will be run to assess serum BDNF concentrations.

  baseline, pre-intervention/procedure/surgery, and immediately after the intervention/procedure/surgery

Secondary Outcomes (1)

• Cognition

  baseline, pre-intervention/procedure/surgery, and immediately after the intervention/procedure/surgery

Study Arms (2)

Ketosis Trial

EXPERIMENTAL

Participants will be given a sugar-free electrolyte mixture with d-beta-hydroxybutrate to drink in a 1:1 ratio calculated to 0.1816g/lb based on body weight before the treadmill test.

Drug: d-beta-hydroxybutrate

Placebo Trial

PLACEBO COMPARATOR

Participants consume a placebo consisting of a pure sugar-free electrolyte drink before treadmill test. The grams of placebo will be calculated 0.1816g/lb based on body weight.

Drug: Placebo

Interventions

d-beta-hydroxybutrate DRUG

During the ketosis trial, participants will be given d-beta-hydroxybutrate mixed with sugar-free gatorade in a 1:1 ratio. This is to ensure the participant's electrolytes are high and to mask the bitter taste of d-beta-hydroxybutrate. The dosage per participant will be calculated 0.1816g/lb based on body weight to ensure participants remain in a state of ketosis for a minimum of 2 hours.

Also known as: Ketosis Supplement

Ketosis Trial

Placebo DRUG

Participants will consume a placebo consisting of a pure electrolyte drink.

Placebo Trial

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy young adults
• years old to 35 years old
• give informed consent

You may not qualify if:

• Diabetics
• history of low blood sugar
• limited physical abilities unable to participate in an aerobic treadmill test

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

University of Southern California

Los Angeles, California, 90089, United States

Location

MeSH Terms

Conditions

Motor Activity; Ketosis

Condition Hierarchy (Ancestors)

Behavior; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Anamika Nanda

CONTACT

4254639902; anamikan@usc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 12, 2025
• First Posted: October 20, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)