Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus

Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 3

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Dehydroepiandrosterone; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 50
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 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; 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.; Other Names: DHEA
Experimental: 2; 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; 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.; Other Names: DHEA
Experimental: Arm 3 (optional); 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; Placebo oral administration prior to each clamp period x2 on day 1. Hyperinsulinemic hypoglycemia on day 2.
Experimental: Arm 4; 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; Placebo oral administration prior to each clamp period x2 on day 1. Hyperinsulinemic hypoglycemia on day 2.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): October 9, 2018
• Study Completion (Actual): October 9, 2018

Study Registration Dates

• First Submitted: January 16, 2008
• First Submitted That Met QC Criteria: February 5, 2008
• First Posted (Estimate): February 6, 2008

Study Record Updates

• Last Update Posted (Actual): September 12, 2019
• Last Update Submitted That Met QC Criteria: September 10, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: hypoglycemia; dehydroepiandrosterone
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Autonomic Nervous System Diseases; Primary Dysautonomias; Diabetes Mellitus, Type 1; Hypoglycemia; Pure Autonomic Failure; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Dehydroepiandrosterone
• Other Study ID Numbers: HP-00044672-DHEA; R01DK069803-03 (U.S. NIH Grant/Contract)