Brief Summary
The investigators are studying the effects of acarbose on muscle and adipose gene transcription in older adults.
Brief Title
Study of Acarbose in Longevity
Detailed Description
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Aging
Eligibility Criteria
Inclusion Criteria:
* Male
* age \>60 years
* impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
Exclusion Criteria:
* cancer
* heart failure
* Chronic Obstructive Pulmonary Disease (COPD)
* inflammatory conditions
* estimated Glomerular Filtration Rate (eGFR) \<45
* active liver disease
* poorly controlled hypertension
* epilepsy
* 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
* Male
* age \>60 years
* impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
Exclusion Criteria:
* cancer
* heart failure
* Chronic Obstructive Pulmonary Disease (COPD)
* inflammatory conditions
* estimated Glomerular Filtration Rate (eGFR) \<45
* active liver disease
* poorly controlled hypertension
* epilepsy
* 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
Inclusion Criteria
Inclusion Criteria:
* Male
* age \>60 years
* impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
* Male
* age \>60 years
* impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
Gender
Male
Gender Based
false
Keywords
acarbose
aging
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
60 Years
NCT Id
NCT02953093
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
2016-6933
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Study of Changes in Muscle and Fat Gene Transcription With Acarbose Treatment: a Crossover Study
Primary Outcomes
Outcome Description
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.
Outcome Measure
Tissue Gene Expression Using RNA Sequencing (RNA-Seq)
Outcome Time Frame
10 weeks
Secondary Outcomes
Outcome Description
Differences in miRNA expression between acarbose and placebo arms were to have been evaluated. 1 milliliter (mL) of sera collected from the processing of blood samples will be used for miRNA sequencing. miRNA was extracted from the serum samples using miRNeasy kit in accordance with the manufacturer's protocol and miRNA libraries were prepared. Cel-miR-39 mimic was added to each sample before extraction, for normalization, and sequenced using multiplexed single-end sequencing on an Illumina HiSeq2500. miRNA are small, non-coding RNAs that regulate gene expression at a post-transcriptional level. Due to their stability in blood, changes in expression of circulating miRNA may serve as markers for age-related pathologies and investigators have correlated B-lymphocyte miRNA profiles in the plasma associated with exceptional longevity. Read counts were to have been summarized by study arm and statistically analyzed using a Wilcoxon test to compare miRNA expression levels.
Outcome Time Frame
At the end of 10 week treatment period (Visit 4) and at 22 weeks (Visit 6) following enrollment
Outcome Measure
Serum microRNA (miRNA)
Outcome Description
16s rDNA gene sequence expression levels were to have been assessed following the collection of stool samples. A fecal microbiome stool collection kit was provided to participants for self-collection of samples and returned for treatment and analysis. 16s rDNA sequencing was to have been performed to assess bacterial species clustering. Fecal microbial DNA was extracted from the samples and eluted DNA divided into 1 cubic centimeter (cc) aliquots and shipped for 16s rDNA sequencing. The raw 16s sequence data was converted to taxonomic profiles by grouping 16s sequences into Operational Taxonomic Units (OTUs) based on sequence similarity as well as by generating de-novo OTU generation using a de novo OTU-picking tool. A Basic Local Alignment Search Tool (BLAST) was to have been used to analyze each OTU's representative against a database. Relative abundance plots for visual comparison of microbial abundances were to have been generated, summarized, and reported by study arm.
Outcome Time Frame
At the end of 10 week treatment period (Visit 4) and at 22 weeks (Visit 6) following enrollment
Outcome Measure
Fecal Microbiome for 16s Ribosomal DNA (rDNA) Gene Sequencing
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
60
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nir Barzilai
Investigator Email
nir.barzilai@einsteinmed.org
Investigator Phone