Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus

University of Maryland Baltimore (UMB)

Status and phase: Completed; Early Phase 1

Conditions: Type 1 Diabetes

Treatments: Drug: Placebo; Drug: Dehydroepiandrosterone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00607646

R01DK069803-03 (U.S. NIH Grant/Contract)

HP-00044672-DHEA

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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50 participants in 4 patient groups

1

Experimental group

Description:

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.

Treatment:

Drug: Dehydroepiandrosterone

2

Experimental group

Description:

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.

Treatment:

Drug: Dehydroepiandrosterone

Arm 3 (optional)

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Arm 4

Experimental group

Description:

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.

Treatment:

Drug: Placebo