Insulin ResistancePhase 2NCT05713799
Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity
A Phase 2 study testing Alpha-lipoic acid and Mirabegron in people with Insulin Resistance and Obesity, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Background: Obesity and related illnesses cause at least 2.8 million deaths each year worldwide. Few treatments exist for obesity that are safe and widely available. A study drug (mirabegron [MG]) combined with a supplement (alpha-lipoic acid [ALA]) may help. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Obesity
- What is being tested?
- Alpha-lipoic acid and Mirabegron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2026to 1 Mar 2030
- Phase
- Phase 2
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- To be eligible to participate in this study, an individual must meet all of the following criteria:
- Adults 18 to 65 years of age
- BMI greater than or equal to 30 kg/m^2 and less than or equal to 45 kg/m^2
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Hypersensitivity and associated allergic reactions to mirabegron or alpha-lipoic acid (or similar drug substances or components).
- Abnormal bladder function, diagnosis of bladder outlet obstruction, urgency, and urinary frequency or use of antimuscarinic medication to treat overactive bladder (OAB).
- Type 1 diabetes mellitus; type 2 diabetes mellitus; or any person taking exogenous insulin therapy or any medication that is a hypoglycemic agent. (type 1 or Type 2 Diabetes mellitus, fasting serum glucose >125 mg/dL, and/or an HbA1c test >6.5%).
- Elevated resting blood pressure >140/90 mmHg.
- Individuals with eGFR <60 ml/min/1.72 m^2 and a urinary albumin/creatinine ratio UACR>300 mg/g.
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- Hypo- or hyper-thyroid disease (TSH >5.0, or <0.4 MIU/L) that is controlled for less than one year or someone currently taking thyroid hormone replacement.
- Anemia, defined by hemoglobin <11.5 g/dL (females) or <13.5 g/dL (males); sickle cell anemia or other blood disorders; and/or wound healing problems.
- Cardiovascular disease, cardiac arrhythmias, orthostasis, unstable vasomotor system, or renal impairment.
- A clinically significant abnormal ECG and/or QTc interval above normal
- Moderate hepatic impairment (Child-Pugh Class B) or above
- Elevated liver enzymes >75 U/L (ALT or AST)
- Recent history in last 4 weeks of any local or systemic infectious disease with fever or requiring antibiotics
- Pregnancy, childbirth within the last year, or breastfeeding in the past 12 months.
- Individuals that have been on a very low-calorie diet (<800 kcal/d), self-reported weight loss >5% in the preceding six months, or those taking weight loss medications.
- History of seizure disorder.
- Addiction to alcohol or substances of abuse within the last 5 years.
- Self-reported current alcohol consumption of more than 2 servings of alcohol per day.
- Self-reported current use of nicotine and/or tobacco products.
- Current use of any drugs known to:
- Have major drug-drug interactions with mirabegron or alpha-lipoic acid
- Be CYP2D6 substrates
- Prolong QT interval
- Alter glucose metabolism or cause insulin resistance (in last six months)
- Treat diabetes mellitus
- Treat hypertension
- Be drugs of abuse
- Inability to provide informed consent.
- Unwilling or unable to eat metabolic meals, as determined by dietitian consult.
- Individuals with significant medical comorbidities or other factors that would render the individual s participation unsafe or affect the outcome of the study as assessed by the investigator.
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
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Phase II Trial of the Combination of Alpha-lipoic Acid and Mirabegron in Women and in Men With Obesity
Background:
Obesity and related illnesses cause at least 2.8 million deaths each year worldwide. Few treatments exist for obesity that are safe and widely available. A study drug (mirabegron [MG]) combined with a supplement (alpha-lipoic acid [ALA]) may help.
Read more
Objective:
To learn how MG and ALA can help the body process food.
Eligibility:
People aged 18 to 65 years with a body mass index between 30 and 45 kg/m2.
Design:
Participants will be screened. They will have a physical exam. They will have blood and urine tests and a test of their heart function. They will speak with a dietician.
The study has two phases. Each phase begins with a 2-day stay in the clinic; then the participant will take the study drugs at home for about 4 weeks, followed by another 2-day stay in the clinic. They will also have outpatient visits about 2 weeks after each clinic stay.
During the clinic stays, participants will undergo many tests:
They will have a plastic tube (catheter) inserted into a vein in each arm. These will be used to draw blood and to infuse glucose (sugar) and insulin.
They will have imaging scans.
They will have a clear hard plastic shield placed over their head to measure oxygen and carbon dioxide as they breathe.
Participants will take the study drugs at home. Both MG and ALA are taken by mouth with water. During one phase, participants will take MG plus a placebo. A placebo looks like the study drug but doesn t contain medicine....
Read the detailed description
Study Description:
This is a single site, Phase II single-blinded, randomized placebo control crossover pilot study. This study aims to explore the effect of adding alphalipoic acid (ALA) to mirabegron (MG) on glucose metabolism and lipolysis rate. Participant target enrollment of 48 total otherwise healthy women (n=24) and men (n=24) with obesity who will be given one of two dosing assignments: MG 50 mg/d and ALA 2400 mg/d or MG 50 mg/d + placebo over 4 weeks followed by a 4-26-week washout period, after which time participant cross over to the opposite dosing assignment. Participants will undergo metabolic testing, safety assessments, and imaging before and after each of the two arms are completed. Women and men will be studied separately using the same protocol.
We hypothesize that in women and in men with obesity (BMI 30-45 kg/m^2), the increases in insulin sensitivity and beta3-AR agonist-induced lipolysis before and after four weeks of taking the dosing assignment will be higher in participants taking the combination MG 50 mg/d and ALA 2400 mg/d compared to taking MG 50 mg/d +placebo.
-Of note, based on our preliminary data and reports in the literature, a key secondary hypothesis is that in women and in men with obesity (BMI 30-45 kg/m^2), the increases in beta3-AR agonist-induced lipolysis before and after four weeks of dosing will be higher in participants taking the combination MG 50 mg/d and ALA 2400 mg/d compared to taking MG 50 mg/d + placebo.
Objectives:
- Primary objective: To compare the change in insulin sensitivity before and after four weeks of taking the combination of the MG 50 mg/d and ALA 2400 mg/d) compared to taking MG 50 mg/d + placebo.
- Secondary objectives:
- Assess the rate of steady-state whole-body lipolysis measured as the rate of isotope appearance (Ra) of [2H5] glycerol before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d+ placebo.
- Determine serum lipids levels before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d + placebo
- To determine the safety and tolerability of the combination of mirabegron (MG) at a dose of 50mg/d with alpha-lipoic acid (ALA) at a dose of 2400 mg/d.
- Assess adipose tissue inflammation and serum inflammatory markers before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d+ placebo.
Endpoints:
- Primary Endpoint: the changes in the Insulin Sensitivity Index (SI) obtained from the FSIGT.
- Secondary Endpoints:
- Maximum observed plasma concentration of ALA and mirabegron (Cmax), time to maximum observed plasma concentration of ALA (Tmax), and area under the concentration-time curve from 0 to 6 hours post-dose.
- Changes in adipose tissue local inflammation before and on dosing assignments will be compared between the two study arms.
- Changes in serum cytokines before and after the dosing assignments will be compared between the two study arms.
- Changes in plasma lipids before and after dosing assignments will be compared between the two study arms.
- The rate of steady-state whole-body lipolysis measured as the rate of isotope appearance (Ra) of [2H5] glycerol before and on dosing assignments will be compared between the two study arms.
- Tertiary/Exploratory Endpoints:
- Assess the resting metabolic rate (RMR) before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d+ placebo
- Assess body composition before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d + placebo
- Assess changes in glucose turnover using labeled glucose and water before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d + placebo
- Assess liver inflammation and fat content by FibroScan(R) before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d+ placebo
- Determine serum levels of metabolic molecules and hormones before and on MG 50 mg/d and ALA 2400 g/d compared to MG 50 mg/d + placebo
- Conditions
- Insulin Resistance, Obesity
- Being tested
- Alpha-lipoic acid, Mirabegron, Placebo
- Keywords
- Obesity, Insulin Sensitivity, Insulin Resistance, Placebo
- Medical subject headings
- Insulin Resistance, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha-lipoic acidDrug
ALA (2.4g) is in a capsule taken twice per day, once in the morning and once in the evening.
MirabegronDrug
Mirabegron (50mg) is a yellow pill taken once per day in the morning.
PlaceboDrug
Placebo will be visibly similar to ALA capsules. They are off-white, clear vegetable-based capsules containing an inert microcrystalline cellulose powder.
| Study group | Role | What they receive |
|---|---|---|
| ALA then placebo | Experimental | Participants receive 50mg/day MG and 2.4g/day ALA (taken in two doses, once in the morning and once in the evening). Then, after a 4-26 week washout period, participants receive 50mg/day MG and twice a day (morning and evening) placebo. Receives: Drug: Alpha-lipoic acid; Drug: Mirabegron; Drug: Placebo |
| Placebo then ALA | Experimental | Participants receive 50mg/day MG and twice a day (morning and evening) placebo. Then, after a 4-26 week washout period, participants receive 50mg/day MG and 2.4g/day ALA (taken in two doses, once in the morning and once in the evening). Receives: Drug: Alpha-lipoic acid; Drug: Mirabegron; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the Insulin sensitivity index (SI) obtained from FSIGT, in (mU/L)^-1 * min^-1
Change in the Insulin sensitivity index before and after 4 weeks of MG and ALA minus change in the insulin sensitivity index before and after 4 weeks of MG and placebo. This measures a change in insulin sensitivity index following ALA while controlling for changes in insulin sensitivity index due to placebo.Delta SI = (SI after ALA - SI before ALA)- (SI after placebo - SI before placebo)
Measured: Insulin sensitivity index measured before and after each intervention in sequence
Secondary outcomes (7)
Maximum observed plasma concentration of ALA (Cmax)
Maximum observed plasma concentration of ALA in ug/mL, measured in serial blood sampling conducted in first 6 hours following MG+ALA dose at study visit
Measured: 0-6 hours after dose of MG+ALA
Time to maximum observed plasma concentration of ALA (Tmax)
Tmax of ALA in minutes, measured in serial blood sampling conducted in first 6 hours following MG+ALA dose at study visit
Measured: 0-6 hours after dose of MG+ALA
Area under the concentration-time curve for ALA
AUC calculated by measuring ALA concentrations in serial blood samples taken in first 6 hours following MG+ALA dose at study visit
Measured: 0-6 hours after dose of MG+ALA
Changes in adipose tissue local inflammation in adipose tissue biopsy samples
Calculated as number of macrophages per high-power fieldChange in inflammation = (macrophages after ALA - macrophages before ALA) - (macrophages after placebo - macrophages before placebo)
Measured: Measured before and after each intervention in sequence
Changes in serum cytokines
Measured in ug/mL of serumChange in cytokines = (cytokine concentration after ALA - cytokine concentration before ALA) - (cytokine concentration after placebo - cytokine concentration before placebo)
Measured: Measured before and after each intervention in sequence
Changes in plasma lipids
Measured in uMol of lipids in plasma samplesChange in lipids = (lipid concentration after ALA - lipid concentration before ALA) - (lipid concentration after placebo - lipid concentration before placebo)
Measured: Measured before and after each intervention in sequence
Changes in the rate of steady-state whole-body lipolysis
Measured as the rate of isotope appearance (Ra) of [2H5] glycerol in plasma, with units of mg/kg/minChange in Ra = (Ra after ALA - Ra before ALA) - (Ra after placebo - Ra before placebo)
Measured: Measured before and after each intervention in sequence
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2023
- Study start28 Oct 2026 (estimated)
- Primary completion1 Mar 2030 (estimated)
- Study completion1 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Aaron M Cypess, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05713799
- Sponsor's protocol ID
- 10000220
- Other IDs
- 000220-DK
- Status last verified
- 23 Sep 2026
- First submitted
- 3 Feb 2023
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided