Testing Glial Pathways to HAAF in Human Subjects Using Carbon 13 Magnetic Resonance Spectroscopy (GLIMpSE)

June 28, 2021 updated by: David McDougal, Pennington Biomedical Research Center
Hypoglycemia-associated autonomic failure (HAAF), a condition commonly developed in diabetic patients, which causes them to have severely low blood sugar levels. This condition makes clinical management of blood sugar in diabetic patients very challenging. This research seeks to better understand how diabetic patients develop HAAF, and what can be done to prevent it.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Following the detection of severe hypoglycemia by the central nervous system (CNS), a series of physiological countermeasures are triggered which return serum glucose to euglycemic levels. This vital homeostatic response frequently becomes dysfunctional in both type 1 and type 2 diabetics, leaving them particularly vulnerable to life threatening bouts of hypoglycemia. This dysfunction, often termed hypoglycemia-associated autonomic failure (HAAF), is thought to be caused by maladaptive changes in the CNS. Currently, progress towards rectifying this HAAF is severely hindered by a lack of knowledge regarding the exact nature of these maladaptive changes and the antecedent events which cause them. Previous work by the PI, as well as others, has identified altered glial metabolism as a potential biological substrate driving HAAF. The alterations in glial metabolism associated with HAAF are strikingly similar to those induced by prolonged dietary restriction in rodents. This raises the intriguing possibility that HAAF may be driven by glial adaptations, normally induced only by prolonged starvation, which are triggered in diabetic individuals by treatment-induced exposure to severe hypoglycemia. The primary goal of our pilot project is to conduct a prospective observational study in humans to test the hypothesis that prolonged fasting will induce changes in glial metabolism similar to those previously measured in individuals with HAAF. The investigators will accomplish this goal via the following specific aims: Aim 1: Using a prospective observational study design in humans, test whether a 72 hour fast will induce acute alterations in glial metabolism, Aim 2: Determine if changes in plasma glucose and leptin levels following prolonged fasting are correlated with changes in glial adaptation. The investigators will utilize innovative 13C magnetic resonance spectroscopy to measure alterations in glial metabolism and substrate preference following acute dietary restriction in healthy young individuals. By demonstrating that metabolic adaptations of glial cells induced by prolonged fasting are similar to those previously associated with HAAF, the investigators can provide key insights into the precursors that may lead to the development of HAAF in diabetic individuals.

Study Type

Observational

Enrollment (Actual)

6

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
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70808-4124
        • Pennington Biomedical Research Center

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

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

Healthy Men

Description

Inclusion Criteria:

  • Male
  • BMI 20.0-24.9 kg/m2
  • 18-40 years old
  • Willing to reside at Pennington Biomedical for 4 days

Exclusion Criteria:

  • Type 1 diabetes mellitus
  • Type 2 diabetes mellitus
  • Fasting glucose ≥ 110 mg/dL (determined at screening visit)
  • Hyperketonuria >15 mg/dL, (determined at screening visit)
  • Contraindication to MRI
  • History of or current eating disorder
  • History of obsessive compulsive disorder
  • Current use of any medication (excluding over-the-counter pain medication)
  • Contraindication to prolonged fasting
  • Consume >10 alcoholic drinks/week

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Healthy Men
Behavioral: Fasting
72 hour fasting

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percent Enrichment of Bicarbonate as Measured by Magnetic Resonance Spectroscopy (MRS)
Time Frame: 80 hours
80 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
Cerebral Metabolic Rate of Acetate Ascertained Through Mathematical Modeling of MRS Data
Time Frame: 80 hours
80 hours
Astroglial TCA Cycle Rate Ascertained Through Mathematical Modeling of MRS Data
Time Frame: 80 hours
80 hours
Glucose Level
Time Frame: 72 hours
72 hours
Change in Leptin Levels
Time Frame: 72 hours
72 hours

Collaborators and Investigators

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

Sponsor

Pennington Biomedical Research Center

Investigators

  • Principal Investigator: David McDougal, PhD, Pennington Biomedical Rsrch Ct

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

February 1, 2016

Primary Completion (Actual)

March 27, 2017

Study Completion (Actual)

July 1, 2017

Study Registration Dates

First Submitted

January 27, 2016

First Submitted That Met QC Criteria

February 18, 2016

First Posted (Estimate)

February 24, 2016

Study Record Updates

Last Update Posted (Actual)

July 19, 2021

Last Update Submitted That Met QC Criteria

June 28, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PBRC 2015-019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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