Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity

NCT05713799 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10000220000220-DK
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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....

Conditions

Insulin Resistance; Obesity

Keywords

Obesity; Insulin Sensitivity; Insulin Resistance; Placebo

Outcome Measures

Primary Outcomes (1)

• 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)

  Insulin sensitivity index measured before and after each intervention in sequence

Secondary Outcomes (7)

• Maximum observed plasma concentration of ALA (Cmax)

  0-6 hours after dose of MG+ALA

• Time to maximum observed plasma concentration of ALA (Tmax)

  0-6 hours after dose of MG+ALA

• Area under the concentration-time curve for ALA

  0-6 hours after dose of MG+ALA

• Changes in adipose tissue local inflammation in adipose tissue biopsy samples

  Measured before and after each intervention in sequence

• Changes in serum cytokines

  Measured before and after each intervention in sequence

Study Arms (2)

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.

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).

Drug: Alpha-lipoic acid; Drug: Mirabegron; Drug: Placebo

Interventions

Alpha-lipoic acid DRUG

ALA (2.4g) is in a capsule taken twice per day, once in the morning and once in the evening.

ALA then placebo; Placebo then ALA

Mirabegron DRUG

Mirabegron (50mg) is a yellow pill taken once per day in the morning.

ALA then placebo; Placebo then ALA

Placebo DRUG

Placebo will be visibly similar to ALA capsules. They are off-white, clear vegetable-based capsules containing an inert microcrystalline cellulose powder.

ALA then placebo; Placebo then ALA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Insulin Resistance; Obesity

Interventions

Thioctic Acid; mirabegron

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids

Study Officials

• Aaron M Cypess, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashley M Schmitz, C.R.N.P.

CONTACT

(920) 948-1186; ashley.schmitz@nih.gov

Aaron M Cypess, M.D.

CONTACT

(301) 435-9267; aaron.cypess@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2023
• First Posted: February 6, 2023
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: April 16, 2026

Record last verified: 2026-04-07

Locations

US (1)