NCT01816165: AcT1

Role of Lipotoxicity in Insulin Resistance, Vascular, and Mitochondrial Dysfunction in Type 1 Diabetes

Completed Phase 3 Results posted Last updated 21 December 2021

What this trial tests

Phase 3 trial testing Acipimox in Type 1 Diabetes in 28 participants. Completed in 24 June 2015.

Timeline

1 June 2011

Primary endpoint
24 June 2015

24 June 2015

Quick facts

Lead sponsor	University of Colorado, Denver
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	28
Start date	1 June 2011
Primary completion	24 June 2015
Estimated completion	24 June 2015
Sites	1 location across United States

Drugs / interventions tested

• Acipimox (ACIPIMOX) — full drug profile →
• Placebo

Conditions studied

• Type 1 Diabetes — all drugs for Type 1 Diabetes →

Sponsor

University of Colorado, Denver

Who can join

Adults 25 to 59, any sex, with Type 1 Diabetes. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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
  Evaluate the impact of Non esterified fatty acid (NEFA)-lowering on insulin sensitivity in T1D versus non-DM. Glucose infusion rate is reported normalized to lean body weight in kg and to final insulin concentration. 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
• 24 Hour Mean Fatty Acid Levels
  Time frame: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
  Assesses whether fatty acid level is consistently lowered by acipimox. Mean of fatty acid levels measured 22 times over 24 hours (hourly except 0100 and 0300 hours).
• Percent Flow-mediated Brachial Artery Dilation
  Time frame: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment
  To determine the effects of NEFA lowering and insulin sensitization on endothelial function. Measures percent change in brachial artery diameter with hyperemia after occlusion.
• State 3 Mitochondrial Oxygen Consumption
  Time frame: muscle biopsy on day 7 of each weeklong intervention period; max 16 weeks post enrollment
  Measures skeletal muscle mitochondrial function and effects of acipimox thereon, carbohydrate \& lipid substrates. State 3 is fully active coupled oxygen flux using PMG or PMGS (pyruvate, malate, glutamate, +/- succinate) or OCMS (octanyl carnitine, malate, +/- succinate) as substrates. FCCP is added as an uncoupler to measure maximum possible O2 flux. Higher values reflect better mitochondrial fu

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mitochondrial dysfunction: mechanisms and advances in therapy.
   Zong Y, Li H, Liao P, Chen L, et al · · 2024 · cited 614× · PMID 38744846 · DOI 10.1038/s41392-024-01839-8
2. Pharmacological advances in mitochondrial therapy.
   Singh A, Faccenda D, Campanella M. · · 2021 · cited 88× · PMID 33647769 · DOI 10.1016/j.ebiom.2021.103244
3. Role of mitochondria in physiological activities, diseases, and therapy.
   Wang L, Zhou X, Lu T. · · 2025 · cited 23× · PMID 40536597 · DOI 10.1186/s43556-025-00284-5