A Randomized Double Blinded Study to Examine the Use of N-acetyl Cysteine for the Prevention and Treatment of HAAF in Patients With Type 1 Diabetes

NCT02206152 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Protocol 22498
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, double blind randomized cross over design trial that will compare the impact of N-acetyl cysteine (200 mg) vs. saline infusion during experimental hypoglycemia on day one on the responses to experimental hypoglycemia on day two. 18 participants will be studied twice, 8 weeks apart. On each occasion they will undergo a 2 hour hypoglycemic clamp (target 50 mg/dl) in the morning and in the afternoon on day one and then again on the morning of day 2 and day 3. During the morning clamps, samples will be collected for later measurement of serum epinephrine levels, plasma and red blood cell NAC, cysteine, and glutathione concentrations and GSH/GSSG ratios (redox status), and participants will be asked to complete a hypoglycemia symptom questionnaire

Conditions

Type 1 Diabetes; Hypoglycemia Unawareness

Keywords

Diabetes; Hypoglycemia; Unawareness; HAAF

Outcome Measures

Primary Outcomes (1)

• Difference in Epinephrine Secretion During the Morning Episodes of Hypoglycemia on Days One and Two Under the Two Treatment Conditions

  Epinephrine secretion during hypoglycemia is assessed by collecting blood samples for measurement of epinephrine concentrations at baseline and every 15 minutes during the period of hypoglycemia (starting at point where blood glucose is first \< 55 mg/dl) in the clamp studies done in the mornings of days 1 and 2 of both parts 1 and 2. .

  8-10 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Normal Saline IV infusion given during a controlled hyperinsulinemic hypoglycemic insulin clamp

Drug: Placebo

Treatment with N-Acetyl Cysteine

EXPERIMENTAL

N-acetyl cysteine IV infusion given as a 150 mg/kg loading dose over the first hour and then follow that with a 50 mg/kg maintenance dose infused over the next 4 hours during a controlled hyperinsulinemic hypoglycemic insulin clamp

Drug: N-acetyl cysteine

Interventions

N-acetyl cysteine DRUG

N-acetyl cysteine (or saline) IV infusion given as a 150 mg/kg loading dose over the first hour and then follow that with a 50 mg/kg maintenance dose infused over the next 4 hours during a controlled hyperinsulinemic hypoglycemic insulin clamp

Also known as: NAC

Treatment with N-Acetyl Cysteine

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy controls
• Age 18 - 65 years
• Baseline hemoglobin A1C \<6.0%

You may not qualify if:

• History of stroke, seizures (other than those related to hypoglycemia), arrhythmias, active cardiac disease (all of which could be associated with adverse cardiac or neurological events during hypoglycemia)
• Pregnancy or plan to become pregnant during the study period
• Diagnosis of asthma (increases risk of hypersensitivity reactions to NAC)
• Use of anti-oxidants or drugs that can alter glucose metabolism
• Concomitant medical problems that may prevent the subject from successfully completing the protocol
• Unwillingness to avoid exercise during the 7 days before each part of the study

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota Department of Medicine, Division of Diabetes, Endocrinology and Metabolism

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Hypoglycemia; Unconsciousness

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Elizabeth Seaquist, MD
• Organization: University of Minenesota

chape044@umn.edu

612-624-9176

Study Officials

• Elizabeth Seaquist, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2014
• First Posted: August 1, 2014
• Study Start: February 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: January 31, 2020
• Results First Posted: January 31, 2020

Record last verified: 2020-01

Locations

US (1)