Free Fatty Acids and Vascular Function in Subjects With Diabetes

NCT00153179 | Completed Phase 1 Results

• 1 other identifier: 2005P-000088
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test the hypothesis that reduction in release of free fatty acids from adipocytes will restore insulin-mediated endothelium-dependent vasodilation and skeletal muscle glucose metabolism in subject with type 2 diabetes.

Conditions

Type 2 Diabetes Mellitus

Keywords

insulin resistance; insulin signaling; endothelium-dependent vasodilation

Outcome Measures

Primary Outcomes (2)

• Flow-mediated Dilation After Placebo or Acipimox Treatment Between Healthy Controls and Those With Metabolic Syndrome

  Flow mediated dilation is calculated as follows: A resting arterial diameter measurement is obtained using the average of 10 EKG-gated ultrasound images. Next, an occlusive pressure is applied (using a blood pressure cuff inflated to a suprasystolic pressure)for a period of 5 minutes. After 5 minutes, the cuff is rapidly deflated. This produces a reactive hyperemic response which is captured via ultrasound at 1 minute post cuff deflation (also 10 EKG-gated images averaged). The diameter of the artery following reactive hyperemia is calculated and compared to the resting diameter to obtain a percent dilation. This is flow-mediated dilation.

  7 days

• Difference in Insulin-mediated Skeletal Muscle Glucose Utilization Between Test Agent and Placebo

  Insulin sensitivity (M) is measured by using a hyperinsulinaemic-euglycaemic clamp. Insulin sensitivity (M) was calculated as the average glucose infusion rate (mg/kg of body weight per min) over the last 30 min of the clamp. Higher values indicate better outcomes (more insulin sensitive), while lower values indicate more insulin resistance.

  baseline, 7 days

Study Arms (2)

1

ACTIVE COMPARATOR

Acipimox treatment for 7 days

Drug: acipimox

2

PLACEBO COMPARATOR

placebo treatment for 7 days

Drug: placebo

Interventions

acipimox DRUG

subjects will receive acipimox 250 mg orally every 6 hours (or matching placebo) for 7 days, including a dose at 6am on the morning of the study testing visit

Also known as: Olbetam

1

placebo DRUG

matching placebo

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• type 2 diabetes mellitus (as defined by the National Diabetes Data Group)
• normal cardiovascular exam
• non smoker (for 1 year prior to entry)
• Healthy volunteers
• no known medical problems
• normal cardiovascular exam
• fasting glucose \< 110 mg/dL
• non-smoker (for 1 year prior to entry)

You may not qualify if:

• Type 2 Diabetics
• untreated hypertension (\>140/90 mmHg)
• untreated hypercholesterolemia (LDL \> 75th percentile for age)
• cigarette smoking within 1 year
• neuropathy requiring medication
• nephropathy (\> 300mg/24 hour urinary albumin, or serum creatinine \> 1.4 mg/dL
• abnormal cardiovascular exam
• treatment with thiazolidinedione within 1 year
• post-menopausal women taking hormone replacement therapy
• (Note: subjects taking angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) must stop these medications for 2 weeks prior to taking study drug. If blood pressure rises to \>140/90, subjects will be prescribed an alternative medication or be withdrawn from the study.
• Healthy Volunteers
• abnormal cardiovascular exam
• use of prescription medications
• fasting glucose \> 110mg/dL
• cigarette smoking within 1 year

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

acipimox

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Results Point of Contact

• Title: Mark A. Creager
• Organization: Brigham and Women's Hospital

Mark.A.Creager@hitchcock.org

603-650-8283

Study Officials

• Mark Creager, M.D.

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: September 1, 2005
• Primary Completion: December 1, 2011
• Study Completion: March 1, 2013
• Last Updated: September 25, 2018
• Results First Posted: July 8, 2013

Record last verified: 2018-08

Locations

US (1)