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

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.

Conflict of interest statement

Conflict of Interest. E.S. is consultant for Sanofi, Merck, BMS-AZ, SkyePharma and Locemia. No other potential conflicts of interest relevant to this article were reported

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1

Schematic representation of study protocol. CGM (continuous glucose monitoring), BG (blood glucose), Hypo (hypoglycemia), CBF (cerebral blood flow measurement)

Figure 2

Counterregulatory hormones during pre- and post-treatment hypoglycemic clamps. Data presented as mean ± SD.

Figure 3

Thalamic cerebral blood flow response to hypoglycemia before (top row) and after treatment (bottom row), shown on sagittal (left column) and axial slices (right column) from one representative subject. The cerebral blood flow response is identified by ΔSI(%). The cerebral blood flow response to hypoglycemia was averaged over the thalamic region per each subject, which were then used for statistical comparisons within and among groups.