CognitionPhase 1NCT07218497
Investigating the Evolutionary Impact of Metabolic Flexibility on Physical Activity-Dependent BDNF and Cognition: Insights From the Val66Met Polymorphism
A Phase 1 study testing d-beta-hydroxybutrate in people with Cognition and BDNF, run by University of Southern California at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- What is being tested?
- d-beta-hydroxybutrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2025to 1 May 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy young adults
- 18 years old to 35 years old
- give informed consent
Who cannot join
- Diabetics
- history of low blood sugar
- limited physical abilities unable to participate in an aerobic treadmill test
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Southern California
Los Angeles, California, 90089
Anamika Nanda, 4254639902, anamikananda@outlook.com
Anamika Nanda
About this study
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?
Read more
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.
- Being tested
- d-beta-hydroxybutrate, Placebo
- Keywords
- Cognition, BDNF, Val66Met SNP, Physical Activity, Ketosis
- Medical subject headings
- Motor Activity, Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
d-beta-hydroxybutrateDrug
Also called Ketosis Supplement
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.
PlaceboDrug
Participants will consume a placebo consisting of a pure electrolyte drink.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline, pre-intervention/procedure/surgery, and immediately after the intervention/procedure/surgery
Secondary outcomes (1)
Cognition
RBANS, Repeatable Battery for the Assessment of Neuropsychological Status, will be administered to participants before and after each respective trial day, both placebo and ketosis trials.
Measured: baseline, pre-intervention/procedure/surgery, and immediately after the intervention/procedure/surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2025
- Study start1 Nov 2025 (estimated)
- Primary completion1 May 2027 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CognitionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Raichlen, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07218497
- Sponsor's protocol ID
- APP-24-05903
- Status last verified
- Oct 2025
- First submitted
- 12 Sep 2025
- Last updated
- 20 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: At this time we do not intend to share IPD to protect their anonymity
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Evolutionary Impact of Metabolic Flexibility on Physical Activity-Dependent BDNF and Cognition: Insights From the Val66Met Polymorphism
- ClinicalTrials.gov ID
- NCT07218497
- Acronym / sponsor ID
- APP-24-05903
- Keywords
- Cognition, BDNF, Val66Met SNP, Physical Activity, Ketosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- 1 Nov 2025 (estimated)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 20 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketosis Trial | Experimental | Drug: d-beta-hydroxybutrateParticipants 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. |
| Placebo Trial | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy young adults
- 18 years old to 35 years old
- give informed consent
Key exclusion criteria (3 listed)
- Diabetics
- history of low blood sugar
- limited physical abilities unable to participate in an aerobic treadmill test
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| d-beta-hydroxybutrateAlso: Ketosis SupplementDuring 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. | Drug | Ketosis Trial |
| PlaceboParticipants will consume a placebo consisting of a pure electrolyte drink. | Drug | Placebo Trial |
Primary outcome
Serum BDNF
Time frame: baseline, pre-intervention/procedure/surgery, and immediately after the intervention/procedure/surgery
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.
1 secondary outcome
Cognition
Time frame: baseline, pre-intervention/procedure/surgery, and immediately after the intervention/procedure/surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2025.
- Individual participant dataSharing planned: No. At this time we do not intend to share IPD to protect their anonymity
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing d-beta-hydroxybutrate in people with Cognition and BDNF, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anamika Nanda (4254639902 ext. 01, anamikan@usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum BDNF (time frame: baseline, pre-intervention/procedure/surgery, and immediately after the intervention/procedure/surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2025.