Sleep Apnea, ObstructivePhase 1/2MET-OSANCT04530747
Metabolic Effects of Metformin Therapy in Obstructive Sleep Apnea
A Phase 1/2 study testing Metformin + PAP in people with Sleep Apnea, Obstructive, run by Pennington Biomedical Research Center at 1 site in United States.
Trial summary
The purpose of the study is to see if metformin improves metabolism in patients with obstructive sleep apnea (OSA) using positive airway pressure (PAP) therapy. Metformin is approved by the Food and Drug Administration (FDA) for the treatment and prevention of diabetes. It is not approved for use in patients with OSA. Read more about this study
- Who is it for?
- Ages 35 to 65 years
- Conditions the study is for
- Sleep Apnea, Obstructive
- What is being tested?
- Metformin + PAP
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jan 2021to 30 Nov 2021
- Phase
- Phase 1/2
- 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 35 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Body mass index (BMI) ≥ 30-50 kg/m^2 (inclusive).
- Apnea-Hypopnea Index ≥ 15 events/h.
- Must be able to provide written informed consent.
- Willing to participate and adhere to study procedures (video recorded in-lab sleep studies, positive airway pressure (PAP) treatment, take study drug, have adipose tissue and skeletal muscle biopsies).
- Women of child-bearing potential must agree to use appropriate contraception to avoid pregnancy throughout the study.
- Willing to have blood, as well as adipose and muscle tissue stored for future use.
Who cannot join
- HbA1c > 6.4%.
- Severe or uncontrolled hypertension defined as systolic blood pressure (BP) ≥180 mmHg and/or diastolic BP ≥110 mmHg on the average of three seated measurements after being at rest for at least 5 minutes.
- Significant cardiovascular, hepatic, renal, neurologic, or psychiatric disease as determined by the study physician.
- Pregnancy, breast feeding or planning pregnancy in the coming 4 months.
- Impaired renal function defined as estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2 (estimated with Chronic Kidney Disease Epidemiology Collaboration equation 1 method).
- Known hypersensitivity to metformin.
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- Currently taking a glucose lowering or weight loss medications.
- Current PAP use or use of PAP in the past 6 months.
- Currently taking antihypertensive and lipid-lowering medications known to affect adipose tissue and skeletal muscle metabolism. For example, statins and drugs targeting renin-angiotensin system will not be allowed. However, use of diuretics, beta-blockers, alpha-blockers and calcium channel blockers may be allowed provided the participant is on a stable dose for at least 3 months prior to the study visit.
- Oxygen desaturation index <15 events/h of sleep.
- Any medication or condition that, in the opinion of the medical investigator, could interfere with the study outcomes or put the subject at risk by participating in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Recruiting core Pennington
Baton Rouge, Louisiana, 70808
About this study
The purpose of the study is to see if metformin improves metabolism in patients with obstructive sleep apnea (OSA) using positive airway pressure (PAP) therapy. Metformin is approved by the Food and Drug Administration (FDA) for the treatment and prevention of diabetes. It is not approved for use in patients with OSA.
Read the detailed description
Positive airway pressure (PAP) is standard therapy for obstructive sleep apnea (OSA) but has shown mixed results for improvement of insulin sensitivity and does not reduce cardiovascular (CV) events and mortality, even in patients with established CV disease. Hence, eliminating intermittent hypoxia alone with standard PAP therapy may not be sufficient to restore metabolism. Additional adjunct strategies (such as metformin) known to improve metabolism may be required to reduce metabolic burden and CV risk in OSA patients. The aim of this study is to examine the longitudinal changes in metabolism of OSA patients receiving both PAP and metformin treatment.
The MET-OSA study will last about 4 months. After screening the participants to determine eligibility, baseline study measures will be obtained and the participants will be provided with standard PAP for OSA treatment. Participants will also be randomized to receive either placebo or metformin treatment for 3 months. Compliance to study drug will be determined during monthly follow-up visits. Final study visit will include assessment of all baseline study measures.
- Conditions
- Sleep Apnea, Obstructive
- Being tested
- Metformin + PAP, Placebo oral capsule + PAP
- Keywords
- Obstructive Sleep Apnea, Metformin
- Medical subject headings
- Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin + PAPDrug
Subjects randomized to this arm will receive 500 mg capsules containing metformin extended release (XR). Metformin XR dosing will be 500 mg (1 x 500 mg) every evening (qPM) during Week 1, 1000 mg (2 x 500 mg) qPM during Week 2, 1500 mg (3 x 500 mg) qPM during Week 3, and 2000 mg (4 x 500 mg) qPM from Week 4 onwards.
Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea.
Placebo oral capsule + PAPDrug
Subjects randomized to this arm will receive 500 mg capsules containing placebo. Placebo dosing will be 500 mg (1 x 500 mg) qPM during Week 1, 1000 mg (2 x 500 mg) qPM during Week 2, 1500 mg (3 x 500 mg) qPM during Week 3, and 2000 mg (4 x 500 mg) qPM from Week 4 onwards.
Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea.
| Study group | Role | What they receive |
|---|---|---|
| Metformin + PAP | Experimental | Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea. Receives: Drug: Metformin + PAP |
| Placebo oral capsule + PAP | Placebo comparator | Subjects randomized to this arm will receive placebo matching study drug. Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea. Receives: Drug: Placebo oral capsule + PAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Matsuda Index
Comparison of change in Matsuda Index as determined by 2-h oral glucose tolerance test (OGTT). During OGTT, response to oral 75g glucose intake is determined by measuring insulin and glucose in timed samples obtained at -5, 10, 20, 30, 60, 90 and 120 min. Matsuda index is a commonly used composite index to estimate whole-body insulin sensitivity. Matsuda index is calculated as (10,000/ square root of [fasting glucose X fasting insulin] X [mean OGTT glucose X mean OGTT insulin]). Increase in scores reflect improvement in whole body insulin sensitivity.
Measured: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Secondary outcomes (5)
Changes in Insulin Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)
Comparison of change in insulin AUC (area under the curve) as derived from 2-h oral glucose tolerance test (OGTT). During OGTT, response to oral 75g glucose intake is determined by measuring insulin and glucose in timed samples obtained at -5, 10, 20, 30, 60, 90 and 120 min. 2-h insulin AUC is calculated using trapezoid method. Higher AUC indicates higher insulin secretion.
Measured: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Glucose Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)
Comparison of change in glucose AUC (area under the curve) as derived from 2-h oral glucose tolerance test (OGTT). During OGTT, response to oral 75g glucose intake is determined by measuring insulin and glucose in timed samples obtained at -5, 10, 20, 30, 60, 90 and 120 min. 2-h glucose AUC is calculated using trapezoid method. Higher AUC indicates higher levels of circulating glucose.
Measured: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Insulinogenic Index
Comparison of insulinogenic index derived from the initial 30 min data from the 2-h oral glucose tolerance test (OGTT). Insulinogenic index measures the early insulin response during the oral glucose challenge. The index is calculated as ratio of change in insulin to glucose from 0 to 30 min values derived from OGTT. Decrease in scores reflect improvement in insulin sensitivity.
Measured: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Disposition Index
Comparison of change in disposition index as derived from 2-h oral glucose tolerance test. Disposition index measures beta-cell function and is calculated as product of Matsuda index and Insulinogenic index values. Increase in scores reflect improvement in glucose metabolism.
Measured: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)
Comparison of change in HOMA-IR value derived from fasting insulin and glucose. HOMA-IR is a simple index for insulin resistance based on fasting measures of glucose and insulin which is a commonly used end-point for assessment of insulin resistance in clinical trials. HOMA-IR is calculated as [(fasting insulin X fasting glucose)/ 22.5]. Higher values indicate higher insulin resistance. An increase will suggest a detrimental effect on glucose metabolism. Individuals with HOMA-IR < 5.7% are considered healthy, between 5.7 and 6.4% are considered prediabetic, and more than 6.4% are considered diabetic.
Measured: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2020
- Study start28 Jan 2021
- Primary completion30 Nov 2021
- Study completion30 Nov 2021
Why it stopped: Recall of positive airway pressure (PAP) device.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sleep Apnea, ObstructiveStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pennington Biomedical Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prachi Singh, Pennington Biomedical Research Center
- Investigators
- Prachi Singh, PhD, Principal investigator, Pennington Biomedical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04530747
- Sponsor's protocol ID
- PBRC 2020-033
- Other IDs
- P30DK072476
- Acronym
- MET-OSA
- Status last verified
- Dec 2022
- First submitted
- 25 Aug 2020
- Last updated
- 19 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Zunica ERM, Heintz EC, Dantas WS, Hebert RC, Tanksley M, Beyl RA, Mader EC Jr, Kirwan JP, Axelrod CL, Singh P. Effects of metformin on glucose metabolism and mitochondrial function in patients with obstructive sleep apnea: A pilot randomized trial. Physiol Rep. 2024 Feb;12(3):e15948. doi: 10.14814/phy2.15948.
PubMed 38346816
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Effects of Metformin Therapy in Obstructive Sleep Apnea
- ClinicalTrials.gov ID
- NCT04530747
- Acronym / sponsor ID
- MET-OSA / PBRC 2020-033
- Conditions
- Sleep Apnea, Obstructive
- Keywords
- Obstructive Sleep Apnea, Metformin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recall of positive airway pressure (PAP) device.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Pennington Biomedical Research CenterUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 28 Jan 2021 (actual)
- Primary completion
- 30 Nov 2021 (actual)
- Study completion
- 30 Nov 2021 (actual)
- First posted
- 28 Aug 2020 (actual)
- Results
- Posted 19 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to see if metformin improves metabolism in patients with obstructive sleep apnea (OSA) using positive airway pressure (PAP) therapy. Metformin is approved by the Food and Drug Administration (FDA) for the treatment and prevention of diabetes. It is not approved for use in patients with OSA.
Detailed description
Positive airway pressure (PAP) is standard therapy for obstructive sleep apnea (OSA) but has shown mixed results for improvement of insulin sensitivity and does not reduce cardiovascular (CV) events and mortality, even in patients with established CV disease. Hence, eliminating intermittent hypoxia alone with standard PAP therapy may not be sufficient to restore metabolism. Additional adjunct strategies (such as metformin) known to improve metabolism may be required to reduce metabolic burden and CV risk in OSA patients. The aim of this study is to examine the longitudinal changes in metabolism of OSA patients receiving both PAP and metformin treatment.
The MET-OSA study will last about 4 months. After screening the participants to determine eligibility, baseline study measures will be obtained and the participants will be provided with standard PAP for OSA treatment. Participants will also be randomized to receive either placebo or metformin treatment for 3 months. Compliance to study drug will be determined during monthly follow-up visits. Final study visit will include assessment of all baseline study measures.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin + PAP | Experimental | Drug: Metformin + PAPSubjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance. Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea. |
| Placebo oral capsule + PAP | Placebo comparator | Drug: Placebo oral capsule + PAPSubjects randomized to this arm will receive placebo matching study drug. Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea. |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Body mass index (BMI) ≥ 30-50 kg/m^2 (inclusive).
- Apnea-Hypopnea Index ≥ 15 events/h.
- Must be able to provide written informed consent.
- Willing to participate and adhere to study procedures (video recorded in-lab sleep studies, positive airway pressure (PAP) treatment, take study drug, have adipose tissue and skeletal muscle biopsies).
- Women of child-bearing potential must agree to use appropriate contraception to avoid pregnancy throughout the study.
Key exclusion criteria (11 listed)
- HbA1c > 6.4%.
- Severe or uncontrolled hypertension defined as systolic blood pressure (BP) ≥180 mmHg and/or diastolic BP ≥110 mmHg on the average of three seated measurements after being at rest for at least 5 minutes.
- Significant cardiovascular, hepatic, renal, neurologic, or psychiatric disease as determined by the study physician.
- Pregnancy, breast feeding or planning pregnancy in the coming 4 months.
- Impaired renal function defined as estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2 (estimated with Chronic Kidney Disease Epidemiology Collaboration equation 1 method).
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 |
|---|---|---|
| Metformin + PAPSubjects randomized to this arm will receive 500 mg capsules containing metformin extended release (XR). Metformin XR dosing will be 500 mg (1 x 500 mg) every evening (qPM) during Week 1, 1000 mg (2 x 500 mg) qPM during Week 2, 1500 mg (3 x 500 mg) qPM during Week 3, and 2000 mg (4 x 500 mg) qPM from Week 4 onwards. Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea. | Drug | Metformin + PAP |
| Placebo oral capsule + PAPSubjects randomized to this arm will receive 500 mg capsules containing placebo. Placebo dosing will be 500 mg (1 x 500 mg) qPM during Week 1, 1000 mg (2 x 500 mg) qPM during Week 2, 1500 mg (3 x 500 mg) qPM during Week 3, and 2000 mg (4 x 500 mg) qPM from Week 4 onwards. Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea. | Drug | Placebo oral capsule + PAP |
Primary outcome
Changes in Matsuda Index
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Comparison of change in Matsuda Index as determined by 2-h oral glucose tolerance test (OGTT). During OGTT, response to oral 75g glucose intake is determined by measuring insulin and glucose in timed samples obtained at -5, 10, 20, 30, 60, 90 and 120 min. Matsuda index is a commonly used composite index to estimate whole-body insulin sensitivity. Matsuda index is calculated as (10,000/ square root of [fasting glucose X fasting insulin] X [mean OGTT glucose X mean OGTT insulin]). Increase in scores reflect improvement in whole body insulin sensitivity.
5 secondary outcomes
Changes in Insulin Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Glucose Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Insulinogenic Index
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Disposition Index
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38346816Zunica ERM, Heintz EC, Dantas WS, Hebert RC, Tanksley M, Beyl RA, Mader EC Jr, Kirwan JP, Axelrod CL, Singh P. Effects of metformin on glucose metabolism and mitochondrial function in patients with obstructive sleep apnea: A pilot randomized trial. Physiol Rep. 2024 Feb;12(3):e15948. doi: 10.14814/phy2.15948.
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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.
Prachi Singh, PhD principal investigator
Pennington Biomedical Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Metformin + PAP in people with Sleep Apnea, Obstructive, run by Pennington Biomedical Research Center 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 6 inclusion and 11 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 19 Jan 2023. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 19 Jan 2023). 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?
Changes in Matsuda Index (time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04530747, which also lists 1 linked publication.
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 19 Jan 2023.