Phase II Trial of the Combination of Alpha-lipoic Acid and Mirabegron in Women and in Men With Obesity
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Changes in the Insulin sensitivity index (SI) obtained from FSIGT, in (mU/L)^-1 * min^-1
研究概览
简要总结
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....
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA
- •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
排除标准
- •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.
- •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.
研究组 & 干预措施
ALA then placebo
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.
干预措施: Placebo (Drug)
Placebo then ALA
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).
干预措施: Alpha-lipoic acid (Drug)
Placebo then ALA
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).
干预措施: Placebo (Drug)
ALA then placebo
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.
干预措施: Alpha-lipoic acid (Drug)
ALA then placebo
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.
干预措施: Mirabegron (Drug)
Placebo then ALA
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).
干预措施: Mirabegron (Drug)
结局指标
主要结局
Changes in the Insulin sensitivity index (SI) obtained from FSIGT, in (mU/L)^-1 * min^-1
时间窗: Insulin sensitivity index measured before and after each intervention in sequence
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)
changes in the Insulin sensitivity index (SI) obtained from FSIGT
时间窗: before and after 4 weeks of intervention
changes in the Insulin sensitivity index
次要结局
- Maximum observed plasma concentration of ALA (Cmax), time to maximum observed plasma concentration of ALA (Tmax), and area under the concentration-time curve.(4 weeks after intervention)
- 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)
- Changes in plasma lipids(Measured before and after each intervention in sequence)
- Changes in the rate of steady-state whole-body lipolysis(Measured before and after each intervention in sequence)