Exogenous Ketones for Healthy Subjects

(K-BREATHE Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Johns Hopkins University

Must not be taking: Acetazolamide, SGLT2 inhibitors, Opioids

Disqualifiers: Sleep disorders, Respiratory impairment, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests exogenous ketones, compounds that might improve breathing without dietary changes. Researchers aim to understand how these ketones affect breathing in healthy individuals, particularly at high altitudes or during sleep. Participants will take both the ketones and a placebo (a harmless pill with no effect) in separate sessions to observe any differences. Ideal participants are healthy, not following specific diets like keto, and have no breathing or sleep-related issues. As an Early Phase 1 trial, this research seeks to understand how these ketones work in people, offering participants a chance to explore this potential new treatment.

Will I have to stop taking my current medications?

The trial requires that you cannot be on certain medications like acetazolamide, SGLT2 inhibitors, or daily opioids. If you are taking these, you would need to stop before participating.

Is there any evidence suggesting that exogenous ketones are likely to be safe for humans?

Research has shown that exogenous ketones (EK) are generally safe for healthy adults. One study found that adults used EKs for up to 28 days without serious problems. Another study reported similar results, indicating no major issues for healthy adults. These findings suggest that EKs can be used without major concerns. However, since this trial is in an early stage, the treatment is still being carefully tested for safety in humans. Prospective participants should keep this in mind when considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about exogenous ketones because they offer a novel approach to boosting energy levels and potentially enhancing cognitive function without the need for dietary changes. Unlike traditional methods that rely on a ketogenic diet to increase ketone levels in the body, exogenous ketones provide a direct way to elevate these levels quickly and efficiently. This new mechanism of action could make it easier for people to experience the benefits of ketosis without the strict dietary restrictions usually required.

What evidence suggests that exogenous ketones might be an effective treatment for improving breathing?

Studies have shown that exogenous ketones can boost energy levels and improve some mental functions by increasing the body's ketone levels. Ketones provide energy, especially when sugar levels are low. This energy boost is why researchers are studying them in this trial for improving physical performance and possibly aiding breathing. Although limited research exists specifically on breathing, the energy benefits of exogenous ketones might prove useful in high altitudes or during exercise. Overall, exogenous ketones are considered safe for most people, with only minor side effects reported. Participants in this trial will receive exogenous ketones in one visit and a placebo in another, allowing researchers to compare the effects directly. ^{3 6 7 8 9}

Who Is on the Research Team?

Jonathan C Jun, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for healthy volunteers interested in how exogenous ketones might affect breathing. Specific eligibility criteria are not provided, but typically participants should have no major health issues that could interfere with the study.

Inclusion Criteria

BMI of 18 - 30 kg/m2

Exclusion Criteria

I do not use supplemental oxygen.

Cannot be on a low carbohydrate (<130 g carbohydrate/day) or ketogenic diet, intermittent fasting, or consuming exogenous ketones

Cannot be pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Baseline Visit

Medical history, physical examination, and urine pregnancy test for women under 60. Run-in procedure to confirm taste tolerance of ketone supplement.

1 day

1 visit (in-person)

Session 1

Participants undergo HCVR testing before and after ingesting 40g of Ketone-IQ or placebo. BHB levels measured at baseline, 1 hour, and 2.5 hours post-ingestion.

1 day

1 visit (in-person)

Washout Period

Minimum 48-hour washout period between sessions.

2-14 days

Session 2

Mirrors Session 1 with participants crossing over to the alternate condition (Ketone-IQ or placebo).

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any adverse effects and overall safety after the completion of both sessions.

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Exogenous Ketones

Trial Overview The trial is testing the impact of a compound called 1,3 butanediol (a type of exogenous ketone) on breathing in comparison to a placebo. It's a randomized study where participants will receive both the test compound and placebo at different times.

How Is the Trial Designed?

Group I: Placebo first Experimental Treatment 2 Interventions

Visit 1: Placebo, Visit 2: ketones

Group II: Ketones first Experimental Treatment 2 Interventions

Visit 1: ketones, Visit 2: Placebo

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10103874/

Exogenous ketone supplementation: an emerging tool for ... Existing human studies report that exogenous ketones can lower blood glucose and improve some aspects of cognitive function, highlighting the ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2161831322002654

Utility of Ketone Supplementation to Enhance Physical ... A systematic search was performed for randomized controlled trials that measured physical performance outcomes in response to ingesting exogenous ketone ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03452761

Effects of Exogenous Ketones in Healthy Young Adults The results of this proposed study will determine whether exogenous ketone supplementation can be useful in promoting better body composition, energy levels, ...

4. mdpi.com mdpi.com/1424-8247/18/10/1436

Divergent Hepatic Outcomes of Chronic Ketone ... Conclusions: Chronic hepatic responses to exogenous ketones are highly formulation dependent. KS demonstrated the most favorable safety profile under the tested ...

5. nutrition.bmj.com nutrition.bmj.com/content/6/2/122

Evaluation of the safety and tolerability of exogenous ... Free D-BHB was safe and well-tolerated, with no severe symptoms reported. Minor side effects like gastrointestinal discomfort were rare. No acid-base or ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11009516/

Evaluation of the safety and tolerability of exogenous ketosis ... We evaluated the safety and tolerability of orally administered free D-BHB in a gender and age-balanced sample of 24 asymptomatic and overtly healthy adults. No ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0273230019302703

Safety and tolerability of sustained exogenous ketosis ... We conclude that sustained exogenous ketosis using a ketone monoester is safe and well-tolerated by healthy adults.

8. physoc.onlinelibrary.wiley.com physoc.onlinelibrary.wiley.com/doi/10.1113/EP090430

Exogenous ketone supplementation: an emerging tool for ... Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Regulatory Toxicology ...

9. medrxiv.org medrxiv.org/content/10.1101/2023.06.12.23291298v1.full.pdf

HYDROXYBUTYRATE IN HEALTHY ADULT SUBJECTS evaluating the safety of different exogenous ketones, it is important to consider that some of. 167 the relevant markers, they measured are ...