ObesityEarly Phase 1NCT03349775
Cardiometabolic Disease and Pulmonary Hypertension
A Early Phase 1 study testing Metformin in people with Obesity, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study will investigate if metformin can help people with obesity and high pressures inside their lung blood vessels. Metformin is approved by the U.S. Food and Drug Administration (FDA) to treat diabetes, but metformin is not approved by the FDA to treat pulmonary hypertension. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Obesity
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Nov 2017to 22 Dec 2020
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 30-80 years
- History of obesity and current BMI ≥ 25 kg/ m2 for study volunteers or BMI ≥ 25 kg/ m2 for those with clinically indicated CPET or known HFpEF
- History of Dyspnea (Grade 1 or more)
- Able to provide informed consent and willing to comply with study
Who cannot join
- History of diabetes mellitus
- History of primary pulmonary arterial hypertension
- History of moderate to severe COPD
- History of severe Obstructive Sleep apnea
- History of renal disease (eGFR< 45 mL/min/1.732)
- History of severe liver disease
Show all 18Show fewer
- History of cardiovascular disease (recent heart attack or stroke) except known HFpEF
- History of blood clot in lung
- History of Splenectomy
- History of Active Cancer
- Platelets count of < 75,000
- International normalized ration (INR) of > 1.5
- History of recent anemia (HB < 9g/dL)
- Current use of Metformin
- Prior LVEF < 50% on echocardiogram
- Indication of severe valvular disease on echo
- Pregnant or planning to become pregnant in next 4 months
- History of HIV infection
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
This study will investigate if metformin can help people with obesity and high pressures inside their lung blood vessels. Metformin is approved by the U.S. Food and Drug Administration (FDA) to treat diabetes, but metformin is not approved by the FDA to treat pulmonary hypertension.
This study will examine whether Metformin will improve the high pressure inside lung blood vessels in people who are obese. The study will help understand the effect of metformin on pressures inside lung blood vessels.
Read the detailed description
Obesity can predispose people to develop high pressures inside their lung blood vessels, a condition called pulmonary hypertension, Pulmonary hypertension in turn, can lead to shortness of breath and other health complications such as heart failure. In this study, we seek to identify individuals at risk for the development of high pressures inside lung vessels based on BMI and dyspnea grade 1.
Participants will be screened by echocardiography to estimate pulmonary pressures. Potential participants will undergo invasive cardiopulmonary exercise testing with hemodynamic monitoring, in order to identify individuals with abnormal pulmonary vascular function either at rest or during exercise. Patients who have undergone clinically-indicated cardiopulmonary exercise testing and meet inclusion/exclusion criteria will also be recruited. Those with abnormal pulmonary vascular function will be randomized to receive Metformin or placebo for a total of 3 months under an IND exemption. The primary outcomes include the effect on pulmonary vascular function at rest and during exercise. Secondary outcomes include change in pulmonary artery endothelial cell phenotypes.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
One capsule by mouth twice a day, followed by an increase to two capsules by mouth twice a day for a total of 3 months
PlaceboDrug
One capsule by mouth twice a day, followed by an increase to two capsules by mouth twice a day for a total of 3 months
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Active comparator | Metformin: 500mg twice daily for 1 week, followed by 1g twice daily for a total of 3 months. Receives: Drug: Metformin |
| Placebo | Placebo comparator | Placebo: 500 mgh twice daily for 1 week, followed by 1g twice daily for a total of 3 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary Vascular Hemodynamics (Rest)
The metformin and placebo groups will be compared with respect to resting mean pulmonary artery pressure (mmHg)
Measured: Baseline and 3 months
Pulmonary Vascular Hemodynamics (Exercise)
The metformin and placebo groups will be compared with respect to augmentation of mean pulmonary artery pressure divided by augmentation of cardiac output during cardiopulmonary exercise testing (change in mean PAP divided by change in cardiac output from rest to peak exercise)
Measured: Baseline and 3 months
Secondary outcomes (1)
Effect on Pulmonary Artery Endothelial Cell Phenotypes
We will compare the metformin and placebo groups. Specifically we will examine the following pulmonary artery endothelial cell phenotypes:
(1) activation of phospho-eNOS as detected by immunofluorescence staining
Measured: baseline and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2017
- Study start27 Nov 2017
- Primary completion22 Dec 2020
- Study completion22 Dec 2020
Why it stopped: After discussion with the Data Safety Monitoring Board and NIH, the randomized clinical trial involving metformin vs. placebo is terminated due to slow enrollment in the setting of the COVID-19 pandemic.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Jennifer En-Sian Ho M.D., Massachusetts General Hospital
- Investigators
- Jennifer E Ho, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03349775
- Sponsor's protocol ID
- 2017P001020
- Other IDs
- 1R01HL134893-01A1
- Status last verified
- Dec 2021
- First submitted
- 6 Jun 2017
- Last updated
- 21 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiometabolic Disease and Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT03349775
- Acronym / sponsor ID
- 2017P001020
- Conditions
- Obesity
- Keywords
- Pulmonary Hypertension, BMI, Echocardiography, CPET, 6-minute walk test, Cardio Metabolic disease
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: After discussion with the Data Safety Monitoring Board and NIH, the randomized clinical trial involving metformin vs. placebo is terminated due to slow enrollment in the setting of the COVID-19 pandemic.
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 27 Nov 2017 (actual)
- Primary completion
- 22 Dec 2020 (actual)
- Study completion
- 22 Dec 2020 (actual)
- First posted
- 22 Nov 2017 (actual)
- Results
- Posted 21 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate if metformin can help people with obesity and high pressures inside their lung blood vessels. Metformin is approved by the U.S. Food and Drug Administration (FDA) to treat diabetes, but metformin is not approved by the FDA to treat pulmonary hypertension.
This study will examine whether Metformin will improve the high pressure inside lung blood vessels in people who are obese. The study will help understand the effect of metformin on pressures inside lung blood vessels.
Detailed description
Obesity can predispose people to develop high pressures inside their lung blood vessels, a condition called pulmonary hypertension, Pulmonary hypertension in turn, can lead to shortness of breath and other health complications such as heart failure. In this study, we seek to identify individuals at risk for the development of high pressures inside lung vessels based on BMI and dyspnea grade 1.
Participants will be screened by echocardiography to estimate pulmonary pressures. Potential participants will undergo invasive cardiopulmonary exercise testing with hemodynamic monitoring, in order to identify individuals with abnormal pulmonary vascular function either at rest or during exercise. Patients who have undergone clinically-indicated cardiopulmonary exercise testing and meet inclusion/exclusion criteria will also be recruited. Those with abnormal pulmonary vascular function will be randomized to receive Metformin or placebo for a total of 3 months under an IND exemption. The primary outcomes include the effect on pulmonary vascular function at rest and during exercise. Secondary outcomes include change in pulmonary artery endothelial cell phenotypes.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Active comparator | Drug: MetforminMetformin: 500mg twice daily for 1 week, followed by 1g twice daily for a total of 3 months. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo: 500 mgh twice daily for 1 week, followed by 1g twice daily for a total of 3 months. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 30-80 years
- History of obesity and current BMI ≥ 25 kg/ m2 for study volunteers or BMI ≥ 25 kg/ m2 for those with clinically indicated CPET or known HFpEF
- History of Dyspnea (Grade 1 or more)
- Able to provide informed consent and willing to comply with study
Key exclusion criteria (18 listed)
- History of diabetes mellitus
- History of primary pulmonary arterial hypertension
- History of moderate to severe COPD
- History of severe Obstructive Sleep apnea
- History of renal disease (eGFR< 45 mL/min/1.732)
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 |
|---|---|---|
| MetforminOne capsule by mouth twice a day, followed by an increase to two capsules by mouth twice a day for a total of 3 months | Drug | Metformin |
| PlaceboOne capsule by mouth twice a day, followed by an increase to two capsules by mouth twice a day for a total of 3 months | Drug | Placebo |
Primary outcome
Pulmonary Vascular Hemodynamics (Rest)
Time frame: Baseline and 3 months
The metformin and placebo groups will be compared with respect to resting mean pulmonary artery pressure (mmHg)
Pulmonary Vascular Hemodynamics (Exercise)
Time frame: Baseline and 3 months
The metformin and placebo groups will be compared with respect to augmentation of mean pulmonary artery pressure divided by augmentation of cardiac output during cardiopulmonary exercise testing (change in mean PAP divided by change in cardiac output from rest to peak exercise)
1 secondary outcome
Effect on Pulmonary Artery Endothelial Cell Phenotypes
Time frame: baseline and 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Jennifer E Ho, MD principal investigator
Massachusetts General Hospital
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 Metformin in people with Obesity, run by Massachusetts General Hospital 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 4 inclusion and 18 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: stopped early, as of the sponsor's last update on 21 Jan 2022. 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?
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?
Yes. Results are posted in the registry (first posted 21 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Pulmonary Vascular Hemodynamics (Rest) (time frame: Baseline and 3 months). The study lists 2 primary outcomes in all. 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 21 Jan 2022.