Evaluating the Effects of a Study Medication on Exercise Function in Type 2 Diabetes (AcT2)

Effects of Serum Fatty Acid Lowering on Insulin Sensitivity, Cardiovascular Function, And Exercise Capacity in Non-Insulin Dependent Diabetes

People who are overweight or who have type 2 diabetes mellitus (T2DM) have higher levels of certain fats in their blood. The blood vessels and heart of most of these individuals do not work normally and people with T2DM also have an impaired ability to perform exercise. The purpose of this study is to use the free fatty acid lowering drug, acipimox, to temporarily decrease the level of fat in the bloodstream of people with T2DM and observe the physiological changes to blood vessel function and exercise capacity and insulin sensitivity. This will help the investigators to understand ways of improving blood vessel function and the ability to exercise effectively in people who are overweight or have T2DM.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Acipimox; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sedentary adults not participating in a regular exercise program (≤ one bout of scheduled exercise per week)
• Subjects must have Type 2 Diabetes
• Subjects must be otherwise healthy
• Ages of 30-60 years
• BMI of 25-39 and stable weight for 3 months prior to the start of the study
• Diabetes controlled by diet +/- insulin secretagogues (sulfonylureas or glinides), metformin, or glucose absorption blockers (acarbose).
• Total glycosylated hemoglobin levels (HbA1C) ≤9% (fair control) on current therapy.

Exclusion Criteria:

• Any comorbid condition which could limit exercise performance including Chronic Obstructive Pulmonary Disease (COPD) or asthma
• Concurrent enrollment in an interventional study.
• Any tobacco use either current or within the last year
• Clinically evident distal symmetrical neuropathy, determined by evaluation of symptoms (numbness, paresthesia) and signs (elicited by vibration, pinprick, light touch, ankle jerks), will be excluded.
• Autonomic dysfunction (>20 mm fall in upright BP without a change in heart rate) will be excluded.
• Evidence of ischemic heart disease by history or abnormal resting or exercise electrocardiogram (EKG) (> 1 mm ST segment depression) on screening exercise test.
• Angina or any other cardiovascular, pulmonary or musculoskeletal symptoms
• Presence of systolic blood pressure >190 at rest or >250 with exercise or diastolic pressure >95 at rest or >105 with exercise
• Proteinuria (urine protein >200 mg/dl) or a creatinine > 2 mg/dl, suggestive of severe renal disease
• Proliferative retinopathy
• Insulin, incretin, or glitazone treatment
• Niacin treatment
• History of peptic ulcers
• A history of hereditary angioedema
• C1 esterase deficiency
• Women who are pregnant or breastfeeding
• Use of fibrate drugs

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acipimox; Subjects will take acipimox 250mg (randomized and double-blinded) by mouth four times a day for six days prior to the visit and one dose the morning of study visi	Drug: Acipimox; Subjects will take acipimox 250mg (randomized and double-blinded) by mouth four times a day for six days prior to the visit and one dose the morning of study visit.; Other Names: Olbetam
Placebo Comparator: Placebo; Subjects will take a placebo pill 250mg (randomized and double-blinded) by mouth four times a day for six days prior to the visit and one dose the morning of study visit	Drug: Placebo; Subjects will take a placebo pill 250mg (randomized and double-blinded) by mouth four times a day for six days prior to the visit and one dose the morning of study visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Impact of Acipimox on Exercise Parameters in People With Type 2 Diabetes: VO2 Kinetics	Evaluate the impact of these effects of NEFA-lowering VO2 kinetics as measured by tau2, the time required for VO2 to reach 67% of peak during submaximal exercise.	7 to 9 days
Evaluate the Impact of Acipimox on Exercise Parameters in People With Type 2 Diabetes: Peak VO2	Evaluate the impact of these effects of NEFA-lowering on exercise capacity measured as peak VO2.	7 to 9 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity	Test the hypothesis that lowering of endogenous non-essential fatty acids (NEFA) in diabetic adults will improve insulin sensitivity measured as glucose disposal by hyperinsulinemic euglycemic clamp. Unit of measure is mg/kg of lean body mass/min/microIU of insulin/ml. The unit of measure reflects the rate at which glucose needs to be infused to maintain a normal blood sugar in the setting of a given serum insulin level from an insulin infusion. As such, a higher number means more glucose was needed and indicates greater sensitivity to insulin.	7 to 9 days
Evaluate the Impact of Acipimox on Exercise Parameters in People With Type 2 Diabetes: Peak Heart Rate	Evaluate the impact of these effects of NEFA-lowering on exercise parameters, including VO2 kinetics, peak VO2, peak heart rate, peak power output.	7 to 9 days
Evaluate the Impact of Acipimox on Exercise Parameters in People With Type 2 Diabetes: Power Output at Anaerobic Threshold and at Peak Exercise	Evaluate the impact of these effects of NEFA-lowering on exercise parameters, including VO2 kinetics, peak VO2, peak heart rate, peak power output.	7 to 9 days
Evaluating the Effect of Acipimox on Insulin Sensitivity and Cardiovascular Function: Inflammation	effect of lowering of endogenous non-essential fatty acids (NEFA) in diabetic adults on inflammation (hsCRP)	7 to 9 days
Evaluating the Effect of Acipimox on Insulin Sensitivity and Cardiovascular Function: Endothelial Function	Test the hypothesis that lowering of endogenous non-essential fatty acids (NEFA) in diabetic adults will improve endothelial function measured by flow mediated dilation of the brachial artery.	7 to 9 days
Evaluating the Effect of Acipimox on Insulin Sensitivity and Cardiovascular Function: Cardiac Function	Test the hypothesis that lowering of endogenous non-essential fatty acids (NEFA) in diabetic adults will improve cardiac function: echo measurement of resting ejection fraction	7 to 9 days
Triglycerides		7 to 9 days

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Pfizer; US Department of Veterans Affairs
• Investigators: Principal Investigator: Irene Schauer, M.D., Ph.D., University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): June 5, 2015
• Study Completion (Actual): June 5, 2015

Study Registration Dates

• First Submitted: May 24, 2011
• First Submitted That Met QC Criteria: April 17, 2012
• First Posted (Estimate): April 19, 2012

Study Record Updates

• Last Update Posted (Actual): December 3, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: diabetes; exercise; insulin sensitivity; heart; cardiovascular
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Acipimox
• Other Study ID Numbers: 10-1393

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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