Clinical trial NCT01816165: Effects of Acipimox on Insulin Action, Vascular Function, and Muscle Function in Type 1 Diabetes
Official title: Role of Lipotoxicity in Insulin Resistance, Vascular, and Mitochondrial Dysfunction in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes
Keywords: diabetes
insulin
blood vessel
type 1
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2013-03-22
Enrollment: 28
Sex: ALL
Minimum age (years): 25
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Insulin Sensitivity: M-value From Hyperinsulinemic Euglycemia Clamp Study
timeFrame: day 8 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: 24 Hour Mean Fatty Acid Levels
timeFrame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Percent Flow-mediated Brachial Artery Dilation
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: State 3 Mitochondrial Oxygen Consumption
timeFrame: muscle biopsy on day 7 of each weeklong intervention period; max 16 weeks post enrollment
Secondary outcomes:
measure: Oxidative Stress and Inflammatory Markers: Interleukin 6 (IL6)
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Oxidative Stress and Inflammatory Markers: TNFalpha
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Oxidative Stress and Inflammatory Markers: High-sensitivity C-reactive Protein (hsCRP)
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Oxidative Stress and Inflammatory Markers: Adiponectin
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Oxidative Stress and Inflammatory Markers: Plasminogen Activator Inhibitor (PAI-1)
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Heart Rate Variability
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Arterial Stiffness (PWV)
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Arterial Stiffness (AI)
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Metabolic Markers: Continuous Glucose Monitoring Measures
timeFrame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Metabolic Markers: Mean 24 Hour Triglyceride and Glucose Levels
timeFrame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Metabolic Markers: Insulin
timeFrame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Metabolic Markers: Glycerol
timeFrame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Vascular Markers
timeFrame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
Other outcomes:
measure: Other Mitochondrial Measures: Mito Content and Electron Transport Chain Complexes
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Oxidative Stress and Inflammatory Markers: Exploratory (Not Collected)
timeFrame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
measure: Counterregulatory Hormones
timeFrame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Irene Schauer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: