Healthy VolunteerEarly Phase 1K-BREATHENCT07220122
Impact of Exogenous Ketones on Breathing in Healthy Volunteers
A Early Phase 1 study testing 1,3 butanediol in people with Healthy Volunteer, run by Johns Hopkins University at 1 site in United States.
Trial summary
Exogenous ketones (EK) are compounds that can increase the level of ketones in the body without needing to change what an individual eats. Although EK have been researched mainly in relation to energy and exercise, there haven't been many studies focusing specifically on how EKs affect breathing using well-established… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer
- What is being tested?
- 1,3 butanediol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2026to 3 Sep 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI of 18 - 30 kg/m2
Who cannot join
- No concomitant sleep disorder (e.g. sleep apnea, insomnia, restless leg syndrome, narcolepsy, idiopathic hypersomnia). If there is no known diagnosis of sleep apnea, a STOP-BANG score of 5 or higher is an exclusion.
- No current daytime respiratory impairment such as uncontrolled asthma, or uncontrolled Chronic Obstructive Pulmonary Disease (COPD), pneumonia, interstitial lung disease.
- No known history of chronic renal disease or diabetes (type 1 or type 2).
- No use of 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
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- Cannot be on medications: acetazolamide or Sodium-glucose cotransporter-2 (SGLT2) inhibitor, daily opioid use.
- No history of claustrophobia or panic disorder
- No frequent alcohol intake (more than 1 drink per day on average, or > 10 drinks per week).
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
About this study
Official title: Impact of Exogenous Ketones on Sleep and Breathing in Healthy Volunteers
Exogenous ketones (EK) are compounds that can increase the level of ketones in the body without needing to change what an individual eats.
Although EK have been researched mainly in relation to energy and exercise, there haven't been many studies focusing specifically on how EKs affect breathing using well-established scientific methods. The investigators believe that EK may help improve breathing, which could be beneficial for situations like high altitudes, sleep apnea, and exercise.
To explore how EK might influence breathing, the investigators are conducting a randomized, placebo-controlled crossover study with healthy volunteers.
Read the detailed description
Healthy volunteers will undergo daytime hypercapnic ventilatory response (HCVR) testing before and after ingesting 40g of exogenous ketones or placebo. Circulating ketone levels (beta-hydroxybutyrate) will be measured at baseline, 1 hour, and 2.5 hours after ingestion (immediately before HCVR testing). Studies will require two visits with a minimum of 48 hr. (and up to a max of 14 days) of washout.
The specific ketone product to be tested is 1,3 butanediol (1,3BD) in a commercially available formulation called "Ketone IQ". A taste-matched placebo will also be supplied by the sponsor. 1,3BD is converted by liver metabolism into the ketone body beta-hydroxybutyrate (BHB) and has been utilized in multiple studies.
PROCEDURES:
This is a randomized, single-blind, crossover study. Each participant will complete two testing sessions with a minimum of 48-hour washout period between visits. The single-blind design enables research staff to measure BHB levels and assess pharmacokinetic timing for potential adjustments to procedure timing, while keeping participants blinded to the intervention.
Baseline visit: A medical history and physical examination will be performed. A urine pregnancy screening test will be conducted for women under 60 years of age. A "run-in" procedure will be performed to confirm that participants can tolerate the taste of the ketone supplement. Participants will then be randomized to one of two arms:
- Group A: Visit 1 Ketones, Visit 2 Placebo
- Group B: Visit 1 Placebo, Visit 2 Ketones
Session 1:
HCVR Procedure: Participants will wear a facemask connected to a breathing circuit with a three-way stopcock, allowing inhaled gas to be switched from ambient air to a pre-mixed gas source. A one-way valve will divert exhaled gas to prevent rebreathing. The participant will breathe room air for 3-5 minutes to collect baseline ventilation data. The investigators will then switch to a non-diffusing gas bag containing 7% Carbon Dioxide (CO₂) / 93% O₂ and the participant will breathing this hypercapnic gas until end-tidal CO₂ (ETCO₂) reaches a stable plateau and is maintained (up to 3 minutes, as tolerated).
Exhaled CO₂ and airflow will be continuously monitored using a pneumotachograph to derive tidal volume and respiratory rate. The HCVR slope will be calculated as minute ventilation (L/min) plotted against end-tidal CO₂ (mmHg).
Session Sequence:
- Participants will arrive at the lab after an overnight fast.
- Baseline HCVR testing will be conducted before study product ingestion.
- Participants will ingest 40 g Ketone-IQ or placebo.
- Repeat HCVR testing 2.5 hours post-ingestion.
Capillary BHB levels will be measured at baseline, 1 hour, and 2.5 hours post-ingestion of Ketone-IQ. Participants will not see the BHB levels (so that the placebo condition will be appropriately masked).
Session 2:
This session will mirror Session 1, with participants crossing over to the alternate condition (i.e., Ketone-IQ or placebo), following a minimum 48-hour washout period.
- Conditions
- Healthy Volunteer
- Being tested
- 1,3 butanediol, Placebo
- Keywords
- ketones breathing exogenous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1,3 butanediolDietary supplement
40 mg Ketone-IQ beverage
PlaceboDietary supplement
Placebo (taste matched)
| Study group | Role | What they receive |
|---|---|---|
| Ketones first | Experimental | Visit 1: ketones, Visit 2: Placebo Receives: Dietary Supplement: 1,3 butanediol; Dietary Supplement: Placebo |
| Placebo first | Experimental | Visit 1: Placebo, Visit 2: ketones Receives: Dietary Supplement: 1,3 butanediol; Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hypercapnic Ventilatory Response (HCVR)
Minute ventilation (L/min) while breathing 7% Carbon Dioxide (CO2). Measured once during each visit.
Measured: During each visit, one measurement at baseline, repeated again 2.5 hours after ingesting Ketone-IQ or Placebo
Secondary outcomes (1)
Ketone Level
Beta-hydroxybutyrate (BHB) in millimole (mmol) from blood. Measured 4 times during each visit.
Measured: During each visit measured 4 times (baseline, 1 hour, 2.5 hours post-ingestion)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2025
- Study start12 Mar 2026
- Primary completion3 Sep 2026
- Study completion3 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteerStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Single blind placebo controlled randomized crossover design.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jonathan C Jun, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07220122
- Sponsor's protocol ID
- IRB00517978-2
- Acronym
- K-BREATHE
- Status last verified
- Sep 2026
- First submitted
- 21 Oct 2025
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon request de-identified primary data related to ketone levels and breathing responses will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Exogenous Ketones on Sleep and Breathing in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT07220122
- Acronym / sponsor ID
- K-BREATHE / IRB00517978-2
- Conditions
- Healthy Volunteer
- Keywords
- ketones breathing exogenous
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 12 Mar 2026 (actual)
- Primary completion
- 3 Sep 2026 (actual)
- Study completion
- 3 Sep 2026 (actual)
- First posted
- 23 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.
Exogenous ketones (EK) are compounds that can increase the level of ketones in the body without needing to change what an individual eats.
Although EK have been researched mainly in relation to energy and exercise, there haven't been many studies focusing specifically on how EKs affect breathing using well-established scientific methods. The investigators believe that EK may help improve breathing, which could be beneficial for situations like high altitudes, sleep apnea, and exercise.
To explore how EK might influence breathing, the investigators are conducting a randomized, placebo-controlled crossover study with healthy volunteers.
Detailed description
Healthy volunteers will undergo daytime hypercapnic ventilatory response (HCVR) testing before and after ingesting 40g of exogenous ketones or placebo. Circulating ketone levels (beta-hydroxybutyrate) will be measured at baseline, 1 hour, and 2.5 hours after ingestion (immediately before HCVR testing). Studies will require two visits with a minimum of 48 hr. (and up to a max of 14 days) of washout.
The specific ketone product to be tested is 1,3 butanediol (1,3BD) in a commercially available formulation called "Ketone IQ". A taste-matched placebo will also be supplied by the sponsor. 1,3BD is converted by liver metabolism into the ketone body beta-hydroxybutyrate (BHB) and has been utilized in multiple studies.
PROCEDURES:
This is a randomized, single-blind, crossover study. Each participant will complete two testing sessions with a minimum of 48-hour washout period between visits. The single-blind design enables research staff to measure BHB levels and assess pharmacokinetic timing for potential adjustments to procedure timing, while keeping participants blinded to the intervention.
Baseline visit: A medical history and physical examination will be performed. A urine pregnancy screening test will be conducted for women under 60 years of age. A "run-in" procedure will be performed to confirm that participants can tolerate the taste of the ketone supplement. Participants will then be randomized to one of two arms:
- Group A: Visit 1 Ketones, Visit 2 Placebo
- Group B: Visit 1 Placebo, Visit 2 Ketones
Session 1:
HCVR Procedure: Participants will wear a facemask connected to a breathing circuit with a three-way stopcock, allowing inhaled gas to be switched from ambient air to a pre-mixed gas source. A one-way valve will divert exhaled gas to prevent rebreathing. The participant will breathe room air for 3-5 minutes to collect baseline ventilation data. The investigators will then switch to a non-diffusing gas bag containing 7% Carbon Dioxide (CO₂) / 93% O₂ and the participant will breathing this hypercapnic gas until end-tidal CO₂ (ETCO₂) reaches a stable plateau and is maintained (up to 3 minutes, as tolerated).
Exhaled CO₂ and airflow will be continuously monitored using a pneumotachograph to derive tidal volume and respiratory rate. The HCVR slope will be calculated as minute ventilation (L/min) plotted against end-tidal CO₂ (mmHg).
Session Sequence:
- Participants will arrive at the lab after an overnight fast.
- Baseline HCVR testing will be conducted before study product ingestion.
- Participants will ingest 40 g Ketone-IQ or placebo.
- Repeat HCVR testing 2.5 hours post-ingestion.
Capillary BHB levels will be measured at baseline, 1 hour, and 2.5 hours post-ingestion of Ketone-IQ. Participants will not see the BHB levels (so that the placebo condition will be appropriately masked).
Session 2:
This session will mirror Session 1, with participants crossing over to the alternate condition (i.e., Ketone-IQ or placebo), following a minimum 48-hour washout period.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Single blind placebo controlled randomized crossover design.
| Arm | Type | Receives |
|---|---|---|
| Ketones first | Experimental | Dietary Supplement: 1,3 butanediol, Dietary Supplement: PlaceboVisit 1: ketones, Visit 2: Placebo |
| Placebo first | Experimental | Dietary Supplement: 1,3 butanediol, Dietary Supplement: PlaceboVisit 1: Placebo, Visit 2: ketones |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- BMI of 18 - 30 kg/m2
Key exclusion criteria (9 listed)
- No concomitant sleep disorder (e.g. sleep apnea, insomnia, restless leg syndrome, narcolepsy, idiopathic hypersomnia). If there is no known diagnosis of sleep apnea, a STOP-BANG score of 5 or higher is an exclusion.
- No current daytime respiratory impairment such as uncontrolled asthma, or uncontrolled Chronic Obstructive Pulmonary Disease (COPD), pneumonia, interstitial lung disease.
- No known history of chronic renal disease or diabetes (type 1 or type 2).
- No use of supplemental oxygen.
- Cannot be on a low carbohydrate (<130 g carbohydrate/day) or ketogenic diet, intermittent fasting, or consuming exogenous ketones
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 |
|---|---|---|
| 1,3 butanediol40 mg Ketone-IQ beverage | Dietary supplement | Ketones first, Placebo first |
| PlaceboPlacebo (taste matched) | Dietary supplement | Ketones first, Placebo first |
Primary outcome
Hypercapnic Ventilatory Response (HCVR)
Time frame: During each visit, one measurement at baseline, repeated again 2.5 hours after ingesting Ketone-IQ or Placebo
Minute ventilation (L/min) while breathing 7% Carbon Dioxide (CO2). Measured once during each visit.
1 secondary outcome
Ketone Level
Time frame: During each visit measured 4 times (baseline, 1 hour, 2.5 hours post-ingestion)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
- Individual participant dataSharing planned: Yes. Upon request de-identified primary data related to ketone levels and breathing responses will be shared.
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Screening Protocol
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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. This study is not recruiting at the moment.
Jonathan C Jun, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing 1,3 butanediol in people with Healthy Volunteer, run by Johns Hopkins University 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 1 inclusion and 9 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: finished, as of the sponsor's last update on 28 Sep 2026. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hypercapnic Ventilatory Response (HCVR) (time frame: During each visit, one measurement at baseline, repeated again 2.5 hours after ingesting Ketone-IQ or Placebo). 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 28 Sep 2026.