Study of Changes in Muscle and Fat Gene Transcription With Acarbose Treatment: a Crossover Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Tissue Gene Expression Using RNA Sequencing (RNA-Seq)
研究概览
简要总结
The investigators are studying the effects of acarbose on muscle and adipose gene transcription in older adults.
详细描述
Acarbose, an FDA approved drug for the treatment of type 2 diabetes, has known effects on glucose metabolism. Evidence from mice indicates that acarbose may prolong lifespan. In humans, acarbose improves inflammatory markers and reduces cardiovascular events. Consequently, acarbose is of interest in clinical translational aging research since it may influence fundamental processes that contribute to age-related diseases. The study described herein is an exploratory study to examine the effect of acarbose treatment on the biology of aging in humans. Specifically, the investigators plan to study whether treatment with a 10 week course of acarbose will alter the gene expression profile in adipose tissue and muscle in older adults in pathways that are known to be affected by human aging, in a placebo-controlled crossover study.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 100 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •age >60 years
- •impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
排除标准
- •heart failure
- •Chronic Obstructive Pulmonary Disease (COPD)
- •inflammatory conditions
- •estimated Glomerular Filtration Rate (eGFR) <45
- •active liver disease
- •poorly controlled hypertension
- •recent cardiovascular disease event (last 6 months)
- •inflammatory bowel disease
- •history of bariatric or other gastric surgery
- •cigarette smoking
- •serious substance abuse.
- •Treatment with drugs known to influence glucose metabolism
- •Hypersensitivity to acarbose or any component of the formulation.
- •Treatment with anti-coagulant medications or anti-platelet drugs
研究组 & 干预措施
Acarbose first
Participants will take acarbose three times daily for 10 weeks (titration over 4 weeks, maintenance 6 weeks). After a two week washout, participants will take placebo three times daily for a total of 10 weeks (titration over 4 weeks, maintenance 6 weeks).
干预措施: Acarbose (Drug)
Acarbose first
Participants will take acarbose three times daily for 10 weeks (titration over 4 weeks, maintenance 6 weeks). After a two week washout, participants will take placebo three times daily for a total of 10 weeks (titration over 4 weeks, maintenance 6 weeks).
干预措施: Placebo (Other)
Placebo first
Participants will take placebo three times daily for 10 weeks (titration over 4 weeks, maintenance 6 weeks). After a two week washout, participants will take acarbose three times daily for a total of 10 weeks (titration over 4 weeks, maintenance 6 weeks).
干预措施: Acarbose (Drug)
Placebo first
Participants will take placebo three times daily for 10 weeks (titration over 4 weeks, maintenance 6 weeks). After a two week washout, participants will take acarbose three times daily for a total of 10 weeks (titration over 4 weeks, maintenance 6 weeks).
干预措施: Placebo (Other)
结局指标
主要结局
Tissue Gene Expression Using RNA Sequencing (RNA-Seq)
时间窗: 10 weeks
Difference in gene expression in muscle and abdominal adipose tissue using RNA-Seq were to have been evaluated to assess the effects of absorbed metabolites on tissues. Muscle and adipose are key metabolic tissues that undergo significant age-related changes and play an active role in the pathogenesis of aging. Muscle and abdominal adipose tissue samples were obtained and homogenized with tissue homogenizer. Subsequent mRNA extraction and analysis of gene expression (RNA seq) was conducted using multiplexed 100bp single-end sequencing. Differential expression between samples and after acarbose and after placebo were to have been determined using a negative binomial model approach implemented in the DESeq package. Results were to have been summarized by study arm and subsequently analyzed.
次要结局
- Serum microRNA (miRNA)(At the end of 10 week treatment period (Visit 4) and at 22 weeks (Visit 6) following enrollment)
- Fecal Microbiome for 16s Ribosomal DNA (rDNA) Gene Sequencing(At the end of 10 week treatment period (Visit 4) and at 22 weeks (Visit 6) following enrollment)