Study of Acarbose in Longevity (SAIL)

Study of Changes in Muscle and Fat Gene Transcription With Acarbose Treatment: a Crossover Study

The investigators are studying the effects of acarbose on muscle and adipose gene transcription in older adults.

Study Overview

• Status: Terminated
• Conditions: Aging
• Intervention / Treatment: Drug: Acarbose; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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).	Drug: Acarbose; see arm description; Other Names: Precose; Other: Placebo; See arm description
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).	Drug: Acarbose; see arm description; Other Names: Precose; Other: Placebo; See arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue Gene Expression Using RNA Sequencing (RNA-Seq)	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.	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum microRNA (miRNA)	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.	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	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.	At the end of 10 week treatment period (Visit 4) and at 22 weeks (Visit 6) following enrollment

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: Glenn Foundation for Medical Research
• Investigators: Principal Investigator: Nir F Barzilai, MD, Albert Einstein College of Medicine Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2017
• Primary Completion (Actual): April 20, 2019
• Study Completion (Actual): December 26, 2019

Study Registration Dates

• First Submitted: September 9, 2016
• First Submitted That Met QC Criteria: October 31, 2016
• First Posted (Estimated): November 2, 2016

Study Record Updates

• Last Update Posted (Actual): June 24, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: aging; acarbose
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Acarbose
• Other Study ID Numbers: 2016-6933

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individual participant data to researchers who are not part of the study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No