Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus

• ClinicalTrials.gov Identifier: NCT00607646
• Recruitment Status: Completed
• First Posted: February 6, 2008
• Last Update Posted: September 12, 2019
• Sponsor: University of Maryland, Baltimore
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Stephen N. Davis, MBBS, University of Maryland, Baltimore

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Drug: Dehydroepiandrosterone; Drug: Placebo	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Other
• Official Title: Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 3
• Study Start Date: October 2010
• Actual Primary Completion Date: October 9, 2018
• Actual Study Completion Date: October 9, 2018

Arms and Interventions

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 Name: 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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in level of catecholamines in blood from baseline [ Time Frame: 6 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Maryland

University of Maryland, Baltimore

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

University of Maryland, Baltimore

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Stephen N. Davis, MD; University of Maryland, Baltimore

More Information

• Responsible Party: Stephen N. Davis, MBBS, Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT00607646
• Other Study ID Numbers: HP-00044672-DHEA; R01DK069803-03 ( U.S. NIH Grant/Contract )
• First Posted: February 6, 2008
• Last Update Posted: September 12, 2019
• Last Verified: September 2019

Keywords provided by Stephen N. Davis, MBBS, University of Maryland, Baltimore:

hypoglycemia; dehydroepiandrosterone

Additional relevant MeSH terms:

Pure Autonomic Failure; Diabetes Mellitus, Type 1; Hypoglycemia; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Dehydroepiandrosterone; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs