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

NCT ID: NCT02690168

Last Updated: 2021-07-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

6 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-02-29

Study Completion Date

2017-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetes Complications Hypoglycemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Healthy Men

Fasting

Intervention Type BEHAVIORAL

72 hour fasting

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Fasting

72 hour fasting

Intervention Type BEHAVIORAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Pennington Biomedical Research Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

David McDougal

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

David McDougal, PhD

Role: PRINCIPAL_INVESTIGATOR

Pennington Biomedical Rsrch Ct

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

McDougal DH, Darpolor MM, DuVall MA, Sutton EF, Morrison CD, Gadde KM, Redman LM, Carmichael OT. Glial acetate metabolism is increased following a 72-h fast in metabolically healthy men and correlates with susceptibility to hypoglycemia. Acta Diabetol. 2018 Oct;55(10):1029-1036. doi: 10.1007/s00592-018-1180-5. Epub 2018 Jun 22.

Reference Type DERIVED
PMID: 29931424 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

PBRC 2015-019

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Does What You Eat Affect Your Brain
NCT05626907 COMPLETED NA
Metabolic Imaging of Neurological Disease
NCT06900244 ENROLLING_BY_INVITATION