Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus

Early Phase 1

Completed

• Conditions: Type 1 Diabetes
• Interventions: Drug: Placebo; Drug: Dehydroepiandrosterone

• Registration Number: NCT00607646
• Lead Sponsor: University of Maryland, Baltimore

Brief Summary

Elevations of plasma cortisol, a stress hormone, during prior episodes of low blood sugar (hypoglycemia) appear to be responsible for the deficient responses during subsequent hypoglycemia. Our specific aim is to determine if dehydroepiandrosterone (DHEA), a hormone with anti-corticosteroid actions, can prevent hypoglycemia associated autonomic failure in type 1 diabetic volunteers.

Detailed Description

DHEA is the acronym for dehydroepiandrosterone, a steroid hormone produced naturally from cholesterol in the adrenal glands of males and females. It is also sold as an over-the-counter dietary supplement, and seems to have anticorticosteroid effects. DHEA antagonizes the effects of corticosterone on hippocampal function in rats and reduces responses to neural stress in mice. In our lab we have found that administration of the DHEA to rats during antecedent hypoglycemia, preserves counter-regulatory responses to subsequent hypoglycemia. The purpose of this study is to determine if the same response occurs in humans.

Study Timeline

• Study First Submitted: 2008-01-16
• Study First Submitted QC: 2008-02-05
• Study First Posted: 2008-02-06
• Study Start: 2010-10
• Primary Completion: 2018-10-09
• Study Completion: 2018-10-09
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-10
• Last Update Posted: 2019-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• 28 (14 males, 14 females) Healthy volunteers aged 18-45 yr.
• 28 (14 males, 14 females) Type 1 diabetic patients aged 18-45 yr.
• HbA1c < 11.0%
• Has been diagnosed Type 1 DM
• No major diabetic tissue complications (i.e. history of retinopathy, neuropathy, stasis ulcers, etc)
• Body mass index < 40kg/m-2

Exclusion Criteria

• pregnancy

Medical history-

• Hepatic Failure/Jaundice
• Renal Failure
• Acute Cerebrovascular/ Neurological deficit

Physical Exam-

• Pneumonia
• Fever greater than 38.0 C
• Blood labs according to protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm 3 (optional)	Placebo	Individuals will be asked to return after at least 2 months and repeat the trial they did not complete (for example, placebo if they were in the DHEA trial before). Again Day 1 would consist of two hyperinsulinemic clamps with placebo or DHEA given orally. Day 2 hyperinsulinemic hypoglycemic clamp with oral administration of placebo or DHEA.
Arm 4	Placebo	Following 6 weeks randomized treatment, Day 1 hyperinsulinemic hypoglycemic clamps x 2 with DHEA or placebo dose given prior to each clamp. Day 2 hypoglycemia with prior dose of randomized treatment.
1	Dehydroepiandrosterone	Hyperinsulinemic (high dose insulin) hypoglycemic clamp studies with oral administration of DHEA or placebo prior to each clamp x 2 on day 1. Day 2 hyperinsulinemic hypoglycemia. Participant randomized to either DHEA or placebo for baseline trial (arm 1) and 6 weeks treatment.
2	Dehydroepiandrosterone	Following 6 weeks randomized treatment, Day 1 hyperinsulinemic hypoglycemic clamps x 2 with DHEA or placebo dose given prior to each clamp. Day 2 hypoglycemia with prior dose of randomized treatment.

Primary Outcome Measures

Name	Time	Method
Change in level of catecholamines in blood from baseline	6 weeks

Trial Locations

Locations (1)

University of Maryland, Baltimore; 🇺🇸 Baltimore, Maryland, United States