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 (NAC for HAAF)

January 21, 2020 updated by: University of Minnesota

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study will consist of a screening visit and two 2-day intervention visits separated by approximately 8 weeks.

At the screening visit, informed consent will be obtained, a standardized form will be used to ensure subjects meet inclusion/exclusion criteria, and baseline hemoglobin A1c will be obtained. On arrival, two IVs will be placed and they will be randomized to receive NAC or saline infusion. Baseline blood samples will be drawn for glucose, epinephrine, norepinephrine, cortisol, cysteine and glutathione measurements. Subjects will then be given 25 mg IV diphenhydramine (Benadryl) followed by a 60 minute infusion of NAC (150 mg) or a similar volume of saline between 8 am and 9 am, followed by a four hour infusion of 50 mg of NAC. Thirty minutes after the start of the NAC infusion, a hyperinsulinemic (2.0 mu/kg/min) hypoglycemic (target = 50 mg/dl) clamp protocol will be started. During the morning study, blood samples will be collected every 5 minutes for monitoring of blood glucose levels and every 15 minutes for later measurement of serum epinephrine, norepinephrine, cortisol. Plasma and red blood cells samples will also be collected every 15 minutes for later measurement of NAC, cysteine, glutathione, and GSH/GSSG ratios (redox status). During the final 15 minutes of the morning clamp, subjects will be asked to quantitate their symptoms using a standardized method (13). At the completion of the morning clamp, glucose will be given to return the participant to euglycemia. 2 hours after the end of the morning clamp, a second hyperinsulinemic (2.0 mu/kg/min) hypoglycemic (target = 50 mg/dl) clamp protocol will be followed over two hours. . The afternoon clamp study will proceed as in the morning except that no serum or plasma will be collected except for the monitoring of glucose and collection of samples for subsequent measurement of NAC, cysteine, glutathione, and GSH/GSSG ratios. After the completion of the afternoon clamps, subjects will be returned to euglycemia and fed a meal. They will be discharged home.

At 7 AM the following morning they will under a single 2 hour hyperinsulinemic hypoglycemic stepped clamp (75, 65, 55,45 mg/dl targets) during which blood samples will be collected as on the morning of day 1. Symptom scores will be collected in the final 15 minutes of each step in the clamp.

At the completion of the study on day 2 of Part 1, they will be scheduled to return for Part 2 in 8 weeks. This timing is selected to ensure that female participants are studied at the same phase of the menstrual cycle. During Part 2 they will receive the treatment not provided during Part 1 in a blinded fashion. The rest of the study protocol will be the same as in Part 1.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Department of Medicine, Division of Diabetes, Endocrinology and Metabolism

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Normal Saline IV infusion given during a controlled hyperinsulinemic hypoglycemic insulin clamp
Drug: Placebo
Experimental: Treatment with N-Acetyl Cysteine
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
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
Other Names:
  • NAC

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Difference in Epinephrine Secretion During the Morning Episodes of Hypoglycemia on Days One and Two Under the Two Treatment Conditions
Time Frame: 8-10 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 31, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 1, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 31, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 21, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Protocol 22498

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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