HypoglycemiaNCT04392843
Effect of Fasting on Insulin-induced Hypoglycemia Counterregulation in Healthy Humans
A study testing Fasting and Feeding in people with Hypoglycemia, run by University of Cincinnati at 1 site in United States.
Trial summary
Iatrogenic hypoglycemia is still considered to be the number one barrier to effective glycemic control in patients with type 1 diabetes (T1D). In a previous study, we observed in dogs that liver glycogen content can be a determinant of hormonal and hepatic responses to insulin-induced hypoglycemia. Read more about this study
- Who is it for?
- Ages 21 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypoglycemia
- What is being tested?
- Fasting and Feeding
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Apr 2019to 11 May 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 21 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males and females of any race or ethnicity.
- Aged 21-40 years.
- Fasting glucose lower than 110 mg/dL.
- Non-obese (BMI <28 kg/m2).
- Otherwise healthy as determined by a physician (i.e., no acute or chronic conditions/ illnesses that might have an impact on the results of the study).
Who cannot join
- Pregnant women.
- Cigarette smoking.
- Taking inflammation-targeting steroids (e.g., prednisone).
- Taking medications targeting adrenergic signaling (e.g., beta-blockers, bronchodilators).
- Hematocrit less than 33%.
- Presence of HIV or hepatitis (due to their deleterious effects on the liver).
Show all 9Show fewer
- The presence of cardiovascular or peripheral vascular disease.
- The presence of neuropathy, retinopathy or nephropathy.
- A diagnosis of diabetes (type 1 or type 2) or a detection of the presence of any other disease or condition by one of the study doctors, that would be expected to confound the responses to insulin-induced hypoglycemia or make participation in the study dangerous to the individual.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Cincinnati
Cincinnati, Ohio, 45267-0547
About this study
Iatrogenic hypoglycemia is still considered to be the number one barrier to effective glycemic control in patients with type 1 diabetes (T1D). In a previous study, we observed in dogs that liver glycogen content can be a determinant of hormonal and hepatic responses to insulin-induced hypoglycemia. In the experiments described herein, we will determine if nutritionally-manipulated changes in liver glycogen concentrations have an impact on hypoglycemic counterregulation in non-T1D control subjects.
Read the detailed description
Because patients with type 1 diabetes (T1D) are required to estimate and administer their own insulin requirements, they frequently overestimate their needs. This often leads to debilitating insulin-induced hypoglycemia, which is the number one barrier to the safe, effective management of glycemia in this population. In addition to the difficulty estimating one's own insulin requirements after a meal, counterregulatory hormone responses to hypoglycemia are impaired in patients with T1D, thereby reducing hepatic glucose production (HGP) and increasing the depth and duration of the hypoglycemic episode.
The discovery of ways by which counterregulatory responses to hypoglycemia can be improved is a priority. In previous experiments in the dog, we observed that experimentally decreasing liver glycogen content (using a 4-hour infusion of glucagon into the hepatic portal vein) reduces counterregulatory hormone secretion during insulin-induced hypoglycemia, thereby reducing hepatic glucose production (HGP). Interestingly, people with T1D have low fasting hepatic glycogen concentrations and the accretion of the sugar in the liver throughout the day is also diminished. Therefore, it is of great interest to understand the relationship between fasting, which would lower liver glycogen levels compared to normal caloric intake, and the counterregulatory responses to insulin-induced hypoglycemia. Furthermore, the translational significance of the investigator's previous findings is also of great importance. To these ends, the studies proposed herein will determine the effect of fasting on hypoglycemic counterregulation in healthy, non-T1D subjects. We hypothesize that fasting will diminish the hormonal and hepatic responses to insulin-induced hypoglycemia.
Each subject will undergo two trials; one where they eat an isocaloric breakfast and lunch prior to an insulin-induced hypoglycemic challenge and a second one during which they remain fasted prior to the hypoglycemic challenge. This study design will allow us to assess the relationship between fasting and the counterregulatory responses to insulin-induced hypoglycemia. For these preliminary studies, only healthy subjects will be studied, thereby reducing their complexity (e.g., no overnight inpatient visits or the need to adjust insulin doses during the feeding periods). Upon completion, we intend to study the more metabolically vulnerable T1D patients.
- Conditions
- Hypoglycemia
- Being tested
- Fasting, Feeding
- Keywords
- glucagon, hepatic glucose production, liver glycogen
- Medical subject headings
- Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FastingOther
Subjects remain fasted prior to insulin-induced hypoglycemia.
FeedingOther
Subjects eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.
| Study group | Role | What they receive |
|---|---|---|
| Fasting | Other | Subjects will remain fasted prior to insulin-induced hypoglycemia. Receives: Other: Fasting |
| Feeding | Active comparator | Subjects will eat a normal breakfast and lunch prior to insulin-induced hypoglycemia. Receives: Other: Feeding |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucagon
From plasma
Measured: During intervention
Epinephrine
From plasma
Measured: During intervention
Glucose infusion rate
Required to clamp glucose at 50 mg/dL
Measured: During intervention
Secondary outcomes (2)
Hepatic glucose production
From plasma
Measured: During intervention
Peripheral glucose uptake
From plasma
Measured: During intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2020
- Study start12 Apr 2019
- Primary completion11 May 2023
- Study completion11 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypoglycemiaStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Two subjects will undergo two metabolic studies, one after having remained fasted and one after having eaten breakfast and lunch.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jason Winnick, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04392843
- Sponsor's protocol ID
- 2018-0625
- Status last verified
- Jul 2023
- First submitted
- 8 May 2020
- Last updated
- 12 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Warner SO, Dai Y, Sheanon N, Yao MV, Cason RL, Arbabi S, Patel SB, Lindquist D, Winnick JJ. Short-term fasting lowers glucagon levels under euglycemic and hypoglycemic conditions in healthy humans. JCI Insight. 2023 Jun 22;8(12):e169789. doi: 10.1172/jci.insight.169789.
PubMed 37166980
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Fasting on Insulin-induced Hypoglycemia Counterregulation in Healthy Humans
- ClinicalTrials.gov ID
- NCT04392843
- Acronym / sponsor ID
- 2018-0625
- Conditions
- Hypoglycemia
- Keywords
- glucagon, hepatic glucose production, liver glycogen
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 12 Apr 2019 (actual)
- Primary completion
- 11 May 2023 (actual)
- Study completion
- 11 May 2023 (actual)
- First posted
- 19 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Iatrogenic hypoglycemia is still considered to be the number one barrier to effective glycemic control in patients with type 1 diabetes (T1D). In a previous study, we observed in dogs that liver glycogen content can be a determinant of hormonal and hepatic responses to insulin-induced hypoglycemia. In the experiments described herein, we will determine if nutritionally-manipulated changes in liver glycogen concentrations have an impact on hypoglycemic counterregulation in non-T1D control subjects.
Detailed description
Because patients with type 1 diabetes (T1D) are required to estimate and administer their own insulin requirements, they frequently overestimate their needs. This often leads to debilitating insulin-induced hypoglycemia, which is the number one barrier to the safe, effective management of glycemia in this population. In addition to the difficulty estimating one's own insulin requirements after a meal, counterregulatory hormone responses to hypoglycemia are impaired in patients with T1D, thereby reducing hepatic glucose production (HGP) and increasing the depth and duration of the hypoglycemic episode.
The discovery of ways by which counterregulatory responses to hypoglycemia can be improved is a priority. In previous experiments in the dog, we observed that experimentally decreasing liver glycogen content (using a 4-hour infusion of glucagon into the hepatic portal vein) reduces counterregulatory hormone secretion during insulin-induced hypoglycemia, thereby reducing hepatic glucose production (HGP). Interestingly, people with T1D have low fasting hepatic glycogen concentrations and the accretion of the sugar in the liver throughout the day is also diminished. Therefore, it is of great interest to understand the relationship between fasting, which would lower liver glycogen levels compared to normal caloric intake, and the counterregulatory responses to insulin-induced hypoglycemia. Furthermore, the translational significance of the investigator's previous findings is also of great importance. To these ends, the studies proposed herein will determine the effect of fasting on hypoglycemic counterregulation in healthy, non-T1D subjects. We hypothesize that fasting will diminish the hormonal and hepatic responses to insulin-induced hypoglycemia.
Each subject will undergo two trials; one where they eat an isocaloric breakfast and lunch prior to an insulin-induced hypoglycemic challenge and a second one during which they remain fasted prior to the hypoglycemic challenge. This study design will allow us to assess the relationship between fasting and the counterregulatory responses to insulin-induced hypoglycemia. For these preliminary studies, only healthy subjects will be studied, thereby reducing their complexity (e.g., no overnight inpatient visits or the need to adjust insulin doses during the feeding periods). Upon completion, we intend to study the more metabolically vulnerable T1D patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two subjects will undergo two metabolic studies, one after having remained fasted and one after having eaten breakfast and lunch.
| Arm | Type | Receives |
|---|---|---|
| Fasting | Other | Other: FastingSubjects will remain fasted prior to insulin-induced hypoglycemia. |
| Feeding | Active comparator | Other: FeedingSubjects will eat a normal breakfast and lunch prior to insulin-induced hypoglycemia. |
Who may qualify
- Ages
- 21 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Males and females of any race or ethnicity.
- Aged 21-40 years.
- Fasting glucose lower than 110 mg/dL.
- Non-obese (BMI <28 kg/m2).
- Otherwise healthy as determined by a physician (i.e., no acute or chronic conditions/ illnesses that might have an impact on the results of the study).
Key exclusion criteria (9 listed)
- Pregnant women.
- Cigarette smoking.
- Taking inflammation-targeting steroids (e.g., prednisone).
- Taking medications targeting adrenergic signaling (e.g., beta-blockers, bronchodilators).
- Hematocrit less than 33%.
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 |
|---|---|---|
| FastingSubjects remain fasted prior to insulin-induced hypoglycemia. | Other | Fasting |
| FeedingSubjects eat a normal breakfast and lunch prior to insulin-induced hypoglycemia. | Other | Feeding |
Primary outcome
Glucagon
Time frame: During intervention
From plasma
Epinephrine
Time frame: During intervention
From plasma
Glucose infusion rate
Time frame: During intervention
Required to clamp glucose at 50 mg/dL
2 secondary outcomes
Hepatic glucose production
Time frame: During intervention
Peripheral glucose uptake
Time frame: During intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2023.
- Derived from this study: PubMed 37166980Warner SO, Dai Y, Sheanon N, Yao MV, Cason RL, Arbabi S, Patel SB, Lindquist D, Winnick JJ. Short-term fasting lowers glucagon levels under euglycemic and hypoglycemic conditions in healthy humans. JCI Insight. 2023 Jun 22;8(12):e169789. doi: 10.1172/jci.insight.169789.
- Individual participant dataSharing planned: No
Related trials for Hypoglycemia
RecruitingObservational study
Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
Congenital Disorders of Glycosylation
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingPhase 2
Effect of Mizagliflozin on Hypoglycemia in Patients With Post-Bariatric Hypoglycemia
Postbariatric Hypoglycemia
Not yet recruitingObservational study
Relationship Between Insulin Dose and Complications in Type 1 Diabetes
Diabetes Mellitus, Type 1 Diabetes, Cardiovascular Diseases (CVD)
Recruiting
Closed Loop and Education for Hypoglycemia Awareness Restoration
Diabetes Mellitus, Type 1
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fasting and Feeding in people with Hypoglycemia, run by University of Cincinnati 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 5 inclusion and 9 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 12 Jul 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Glucagon (time frame: During intervention). The study lists 3 primary outcomes in all. 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 NCT04392843, 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 12 Jul 2023.