Diabetes ComplicationsGLIMpSENCT02690168
Testing Glial Pathways to HAAF in Human Subjects Using Carbon 13 Magnetic Resonance Spectroscopy
An observational study of Diabetes Complications and Hypoglycemia, run by Pennington Biomedical Research Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Diabetes Complications, Hypoglycemia
- What is being tested?
- Fasting
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to Jul 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Study population: Healthy Men
Who may be able to join
- Male
- BMI 20.0-24.9 kg/m2
- 18-40 years old
- Willing to reside at Pennington Biomedical for 4 days
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Pennington Biomedical Research Center
Baton Rouge, Louisiana, 70808-4124
About this study
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.
Read the 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.
- Conditions
- Diabetes Complications, Hypoglycemia
- Being tested
- Fasting
- Keywords
- Fasting, Carbon-13 Magnetic Resonance Spectroscopy, Neuroimaging
- Medical subject headings
- Diabetes Complications, Hypoglycemia, Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FastingBehavioural
72 hour fasting
| Study group | Role | What they receive |
|---|---|---|
| Healthy Men | Not described Receives: Behavioral: Fasting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Enrichment of Bicarbonate as Measured by Magnetic Resonance Spectroscopy (MRS)
Measured: 80 hours
Secondary outcomes (4)
Cerebral Metabolic Rate of Acetate Ascertained Through Mathematical Modeling of MRS Data
Measured: 80 hours
Astroglial TCA Cycle Rate Ascertained Through Mathematical Modeling of MRS Data
Measured: 80 hours
Glucose Level
Measured: 72 hours
Change in Leptin Levels
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study startFeb 2016
- Primary completion27 Mar 2017
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes ComplicationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pennington Biomedical Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David McDougal, Pennington Biomedical Research Center
- Investigators
- David McDougal, PhD, Principal investigator, Pennington Biomedical Rsrch Ct
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02690168
- Sponsor's protocol ID
- PBRC 2015-019
- Acronym
- GLIMpSE
- Status last verified
- Jun 2021
- First submitted
- 27 Jan 2016
- Last updated
- 19 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 29931424
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testing Glial Pathways to HAAF in Human Subjects Using Carbon 13 Magnetic Resonance Spectroscopy
- ClinicalTrials.gov ID
- NCT02690168
- Acronym / sponsor ID
- GLIMpSE / PBRC 2015-019
- Conditions
- Diabetes Complications, Hypoglycemia
- Keywords
- Fasting, Carbon-13 Magnetic Resonance Spectroscopy, Neuroimaging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Pennington Biomedical Research CenterUniversity, hospital or other
- Study start
- Feb 2016 (actual)
- Primary completion
- 27 Mar 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 24 Feb 2016 (estimated)
- Results
- Posted 19 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy Men | – | Behavioral: Fasting |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Healthy Men
Key inclusion criteria (4 listed)
- Male
- BMI 20.0-24.9 kg/m2
- 18-40 years old
- Willing to reside at Pennington Biomedical for 4 days
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fasting72 hour fasting | Behavioural | Healthy Men |
Primary outcome
Percent Enrichment of Bicarbonate as Measured by Magnetic Resonance Spectroscopy (MRS)
Time frame: 80 hours
4 secondary outcomes
Cerebral Metabolic Rate of Acetate Ascertained Through Mathematical Modeling of MRS Data
Time frame: 80 hours
Astroglial TCA Cycle Rate Ascertained Through Mathematical Modeling of MRS Data
Time frame: 80 hours
Glucose Level
Time frame: 72 hours
Change in Leptin Levels
Time frame: 72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29931424McDougal 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David McDougal, PhD principal investigator
Pennington Biomedical Rsrch Ct
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Complications and Hypoglycemia, run by Pennington Biomedical Research Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Enrichment of Bicarbonate as Measured by Magnetic Resonance Spectroscopy (MRS) (time frame: 80 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02690168, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2021.