Naltrexone for treatment of impaired awareness of hypoglycemia in type 1 diabetes: A randomized clinical trial

J Diabetes Complications. 2015 Nov-Dec;29(8):1277-82. doi: 10.1016/j.jdiacomp.2015.08.004. Epub 2015 Aug 12.

Abstract

Aims: Impaired awareness of hypoglycemia (IAH) is a limiting factor in the treatment of type 1 diabetes (T1D) and is a challenging condition to reverse. The objective of this study was to test the hypothesis that naltrexone therapy in subjects with T1D and IAH will improve counterregulatory hormone response and recognition of hypoglycemia symptoms during hypoglycemia.

Methods: We performed a pilot randomized double blind trial of 4weeks of naltrexone therapy (n=10) or placebo (n=12) given orally in subjects with T1D and IAH. Outcome measures included hypoglycemia symptom scores, counterregulatory hormone levels and thalamic activation as measured by cerebral blood flow using MRI during experimental hypoglycemia in all subjects before and after 4weeks of intervention.

Results: After 4weeks of therapy with naltrexone or placebo, no significant differences in response to hypoglycemia were seen in any outcomes of interest within each group.

Conclusions: In this small study, short-term treatment with naltrexone did not improve recognition of hypoglycemia symptoms or counterregulatory hormone response during experimental hypoglycemia in subjects with T1D and IAH. Whether this lack of effect is related to the small sample size or due to the dose, the advanced stage of study population or the drug itself should be the subject of future investigation.

Trial registration: ClinicalTrials.gov NCT01053078.

Keywords: HAAF; Hypoglycemia; Impaired awareness of hypoglycemia; Naltrexone; Opioid antagonists; Type 1 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Cerebral Angiography / drug effects
  • Cerebrovascular Circulation / drug effects
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diagnostic Self Evaluation*
  • Double-Blind Method
  • Female
  • Glucose Clamp Technique
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / diagnosis*
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / adverse effects
  • Insulin / therapeutic use*
  • Magnetic Resonance Angiography
  • Male
  • Middle Aged
  • Monitoring, Ambulatory
  • Naltrexone / adverse effects
  • Naltrexone / therapeutic use*
  • Narcotic Antagonists / adverse effects
  • Narcotic Antagonists / therapeutic use*
  • Pilot Projects
  • Thalamus / blood supply
  • Thalamus / drug effects

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Narcotic Antagonists
  • hemoglobin A1c protein, human
  • Naltrexone

Associated data

  • ClinicalTrials.gov/NCT01053078