Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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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
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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.

Official Title
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Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 3

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Dehydroepiandrosterone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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. | Drug: Dehydroepiandrosterone<br>* Placebo tablets or tablets containing DHEA will be given orally before each hyperinsulinemic clamps on day 1 (x 2). Placebo tablets or tablets containing DHEA will be given orally before Day 2 hyperinsulinemic hypoglycemic clamp x 1.<br>* Other names: DHEA;|
| Experimental: 2<br>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. | Drug: Dehydroepiandrosterone<br>* Placebo tablets or tablets containing DHEA will be given orally before each hyperinsulinemic clamps on day 1 (x 2). Placebo tablets or tablets containing DHEA will be given orally before Day 2 hyperinsulinemic hypoglycemic clamp x 1.<br>* Other names: DHEA;|
| Experimental: Arm 3 (optional)<br>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. | Drug: Placebo<br>* Placebo oral administration prior to each clamp period x2 on day 1. Hyperinsulinemic hypoglycemia on day 2.<br>|
| Experimental: Arm 4<br>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. | Drug: Placebo<br>* Placebo oral administration prior to each clamp period x2 on day 1. Hyperinsulinemic hypoglycemia on day 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in level of catecholamines in blood from baseline |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypoglycemia, dehydroepiandrosterone