Overview

This trial is active, not recruiting.

Condition type 1 diabetes
Treatments acipimox, placebo
Phase phase 3
Sponsor University of Colorado, Denver
Start date June 2011
End date January 2017
Trial size 40 participants
Trial identifier NCT01816165, 11-0649, 6181

Summary

Insulin resistance (IR) is an important contributor to increased cardiovascular disease risk in type 1 diabetes (T1D). Non-esterified fatty acid elevation is a significant contributor to IR in T1D and may be a target of intervention. The hypothesis of the study is that isolated fatty acid lowering with acipimox will improve insulin action and blood vessel function and have the benefit of reducing mitochondrial oxidant generation and improving mitochondrial function in T1D. Targeting IR through fatty acid lowering is a novel approach to T1D treatment that may significantly improve current management of TID and of cardiovascular disease (CVD) risk in this high risk population.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model crossover assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Drug: acipimox
acipimox Olbetam
Subjects will take acipimox/placebo 250mg (randomized and double-blinded) by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
(Placebo Comparator)
Drug: Placebo
placebo
Subjects will take acipimox/placebo 250mg (randomized and double-blinded) by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day

Primary Outcomes

Measure
Insulin sensitivity: M-value from hyperinsulinemic euglycemia clamp study
time frame: day 8 of each of the 2 random order intervention phases; max 16 weeks post enrollment
24 hour fatty acid levels (area under the curve)
time frame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
Percent flow-mediated brachial artery dilation
time frame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
State 3 mitochondrial oxygen consumption
time frame: muscle biopsy on day 7 of each weeklong intervention period; max 16 weeks post enrollment

Secondary Outcomes

Measure
Oxidative stress and inflammatory markers
time frame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
Other mitochondrial measures
time frame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
Heart rate variability
time frame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
Arterial stiffness (PWV and AI)
time frame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
Metabolic markers
time frame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Eligibility Criteria

Male or female participants from 25 years up to 59 years old.

Inclusion Criteria: 1. Men and women, with and without type 1 diabetes between 25-59 years of age, 2. HbA1c 6.0-9.5 (T1D only), 3. Subjects who are willing to commit to: - 14 days of prescribed diet, - two 44 hour inpatient stays, and - two muscle biopsies. Exclusion Criteria: 1. Any comorbid condition associated with inflammation, insulin resistance, or dyslipidemia, 2. Tobacco use, 3. Pregnancy, 4. Steroid use, 5. Scheduled physical activity >3 days a week, 6. Angina or any other cardiovascular or pulmonary disease, 7. History of chronic obstructive pulmonary disease or asthma, 8. Systolic blood pressure >190 at rest or >250 with exercise, or 9. Diastolic pressure >95 at rest, or >105 with exercise, 10. Proteinuria (urine protein >200 mg/dl), or 11. Creatinine > 2 mg/dl, suggestive of severe renal disease, 12. Severe Proliferative retinopathy, 13. Niacin treatment, 14. History of peptic ulcers, 15. History of hereditary angioedema, and 16. C1 esterase deficiency.

Additional Information

Official title Role of Lipotoxicity in Insulin Resistance, Vascular, and Mitochondrial Dysfunction in Type 1 Diabetes
Principal investigator Irene Schauer, MD, PhD
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by University of Colorado, Denver.