Type 1 DiabetesNCT00580710
Investigation Into the Effects Upon Brain Response to Change in Circulating Glucose Levels in Diabetes Mellitus
An observational study of Type 1 Diabetes and Hypoglycemia, run by Yale University at 1 site in United States.
Trial summary
This study is designed to investigate the effects of diabetes mellitus and its treatment upon the body's responses to low blood glucose (blood sugar) levels. Diabetes is a medical condition in which blood glucose can rise very high. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes, Hypoglycemia
- How many people
- 164 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2001to 1 Nov 2018
- Phase
- Observational
- 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: The recruited subjects will reflect the gender and ethnic distribution of the Yale and New Haven community. The recruited subjects with type 1 diabetes will reflect the demographics of the clinic population in New Haven. Subject selection is independent of race and sex.
Who may be able to join
- All subjects:
- on a weight maintaining diet
- ability to read and speak English fluently
- For All Type 1 Diabetics all of the above inclusion criteria AND C-peptide negative AND no evidence of neuropathy or proliferative retinopathy
- Only for Type 1 Diabetics in the intensively treated group: HbA1c < 7.5% AND documented hypoglycemia at least once per week over at least 4 weeks of frequent daily self monitoring
- Only for Type 1 Diabetics in the conventionally treated group:HbA1c ≥ 8.5%
- Age 18-40 years in the groups 1,2, and 3. Age 18-50 in groups arm 2 obese and control.
- BMI <30 in the groups 1,2, and 3; BMI >18.4 but < or = 25 in the arm control group; and BMI > or = 30kg/m2 in the obese group.
Who cannot join
- Pregnancy
- History of neurologic or cardiovascular disease
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale University School of Medicine
New Haven, Connecticut, 06520
About this study
This study is designed to investigate the effects of diabetes mellitus and its treatment upon the body's responses to low blood glucose (blood sugar) levels. Diabetes is a medical condition in which blood glucose can rise very high. Treatment of diabetes mellitus involves giving insulin (a hormone), which can occasionally cause blood glucose to fall too low. The body responds to low glucose levels by producing a number of hormones, which act against the insulin to help correct the low blood glucose. These hormones also provide symptoms which warn that the glucose is falling too far. These protective warnings by the body may be different in people with diabetes. We want to test whether this also means that diabetes changes the sensitivity of brain function to a lowering of blood glucose levels. In order to answer this question, we need to compare the response of people with diabetes with the response of people who do not have diabetes.
The plan of the study is to lower the subject's blood glucose using insulin, while measuring what changes occur in brain function using what is called functional magnetic resonance imaging (fMRI).
Read the detailed description
Previous studies have shown that a person with type 1 diabetes is less likely to suffer the long term microvascular complications of diabetes (eye, kidney and nerve damage) if they strive to achieve as near normal a blood glucose as possible. Unfortunately the tighter the blood glucose control is, the more likely the subject is to suffer episodes of hypoglycemia. Hypoglycemia is often the aspect of diabetes management most feared by people with diabetes and may cause more anxiety than the threat of advanced complications.
For many people with diabetes the problem of hypoglycemia is compounded by the development of the syndrome of hypoglycemia unawareness. One aspect of hypoglycemia unawareness is impairment of the hormones normally released as blood glucose falls. Hypoglycemia triggers a release of such insulin antagonists as epinephrine, norepinephrine, glucagon, growth hormone and cortisol. These hormones act synergistically with the autonomic nervous system to raise blood glucose, counteracting insulin and restoring normoglycemia. These homeostatic mechanisms are also responsible for some of the early symptoms of low blood glucose, providing a warning to insulin-treated diabetics as glucose falls. A number of studies including research from this unit have established that strict metabolic control is associated with impairment of the normal counterregulatory response to hypoglycemia and a loss of hypoglycemia awareness.
The brain is central to the recognition of hypoglycemia and the coordination of the counterregulatory response. Neural tissue depends mainly on glucose for its energy supply. As circulating glucose falls beneath the level needed to maintain glucose transport across the blood-brain barrier, a variety of defense mechanisms are activated, including symptoms of cognitive dysfunction. However, the precise nature and causes of the adverse CNS effects of hypoglycemia are not well understood.
Functional magnetic resonance imaging (fMRI) provides a tool to measure the effects of hypoglycemia on the patterns and magnitudes of neuronal activation in the human brain, in both normal and diabetic subjects.
- Conditions
- Type 1 Diabetes, Hypoglycemia
- Keywords
- type 1 diabetes, hypoglycemia, magnetic resonance imaging
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| conventionally treated | conventionally treated, relatively poorly controlled patients with type 1 diabetes | |
| intensively treated | intensively treated, well controlled patients with type 1 diabetes | |
| lean healthy | age- and sex- matched non-diabetic, normal weight (BMI > or = 18.5 but < or = 25 kg/m2) control subjects | |
| obese subjects | obese individuals defined as BMI > or = 30kg/m2 | |
| type 2 diabetics | Type 2 diabetics on diet only or diet and Metformin | |
| type 1 diabetes unaware | Type 1 diabetics unaware of hypoglycemic symptoms | |
| type 1 diabetes aware | Type 1 diabetics aware of hypoglycemic symptoms |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain response to blood glucose levels
Brain response is operationally defined as: fMRI BOLD signal to detect differences in brain activation in response to changes in glucose levels taken between 4 to 8 weeks after subject enrollment.
Measured: 4 to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2007 (estimated)
- Study startAug 2001
- Primary completion1 Nov 2018
- Study completion1 Nov 2018
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 Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert Sherwin, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00580710
- Sponsor's protocol ID
- 0108012609
- Other IDs
- 2R01DK020495-37
- Status last verified
- Apr 2022
- First submitted
- 19 Dec 2007
- Last updated
- 18 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Parikh L, Seo D, Lacadie C, Belfort-Deaguiar R, Groskreutz D, Hamza M, Dai F, Scheinost D, Sinha R, Todd Constable R, Sherwin R, Hwang JJ. Differential Resting State Connectivity Responses to Glycemic State in Type 1 Diabetes. J Clin Endocrinol Metab. 2020 Jan 1;105(1):1-13. doi: 10.1210/clinem/dgz004.
PubMed 31511876
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation Into the Effects Upon Brain Response to Change in Circulating Glucose Levels in Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT00580710
- Acronym / sponsor ID
- 0108012609
- Conditions
- Type 1 Diabetes, Hypoglycemia
- Keywords
- type 1 diabetes, hypoglycemia, magnetic resonance imaging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Aug 2001
- Primary completion
- 1 Nov 2018 (actual)
- Study completion
- 1 Nov 2018 (actual)
- First posted
- 27 Dec 2007 (estimated)
- 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.
This study is designed to investigate the effects of diabetes mellitus and its treatment upon the body's responses to low blood glucose (blood sugar) levels. Diabetes is a medical condition in which blood glucose can rise very high. Treatment of diabetes mellitus involves giving insulin (a hormone), which can occasionally cause blood glucose to fall too low. The body responds to low glucose levels by producing a number of hormones, which act against the insulin to help correct the low blood glucose. These hormones also provide symptoms which warn that the glucose is falling too far. These protective warnings by the body may be different in people with diabetes. We want to test whether this also means that diabetes changes the sensitivity of brain function to a lowering of blood glucose levels. In order to answer this question, we need to compare the response of people with diabetes with the response of people who do not have diabetes.
The plan of the study is to lower the subject's blood glucose using insulin, while measuring what changes occur in brain function using what is called functional magnetic resonance imaging (fMRI).
Detailed description
Previous studies have shown that a person with type 1 diabetes is less likely to suffer the long term microvascular complications of diabetes (eye, kidney and nerve damage) if they strive to achieve as near normal a blood glucose as possible. Unfortunately the tighter the blood glucose control is, the more likely the subject is to suffer episodes of hypoglycemia. Hypoglycemia is often the aspect of diabetes management most feared by people with diabetes and may cause more anxiety than the threat of advanced complications.
For many people with diabetes the problem of hypoglycemia is compounded by the development of the syndrome of hypoglycemia unawareness. One aspect of hypoglycemia unawareness is impairment of the hormones normally released as blood glucose falls. Hypoglycemia triggers a release of such insulin antagonists as epinephrine, norepinephrine, glucagon, growth hormone and cortisol. These hormones act synergistically with the autonomic nervous system to raise blood glucose, counteracting insulin and restoring normoglycemia. These homeostatic mechanisms are also responsible for some of the early symptoms of low blood glucose, providing a warning to insulin-treated diabetics as glucose falls. A number of studies including research from this unit have established that strict metabolic control is associated with impairment of the normal counterregulatory response to hypoglycemia and a loss of hypoglycemia awareness.
The brain is central to the recognition of hypoglycemia and the coordination of the counterregulatory response. Neural tissue depends mainly on glucose for its energy supply. As circulating glucose falls beneath the level needed to maintain glucose transport across the blood-brain barrier, a variety of defense mechanisms are activated, including symptoms of cognitive dysfunction. However, the precise nature and causes of the adverse CNS effects of hypoglycemia are not well understood.
Functional magnetic resonance imaging (fMRI) provides a tool to measure the effects of hypoglycemia on the patterns and magnitudes of neuronal activation in the human brain, in both normal and diabetic subjects.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| conventionally treated | – | –conventionally treated, relatively poorly controlled patients with type 1 diabetes |
| intensively treated | – | –intensively treated, well controlled patients with type 1 diabetes |
| lean healthy | – | –age- and sex- matched non-diabetic, normal weight (BMI > or = 18.5 but < or = 25 kg/m2) control subjects |
| obese subjects | – | –obese individuals defined as BMI > or = 30kg/m2 |
| type 2 diabetics | – | –Type 2 diabetics on diet only or diet and Metformin |
| type 1 diabetes unaware | – | –Type 1 diabetics unaware of hypoglycemic symptoms |
| type 1 diabetes aware | – | –Type 1 diabetics aware of hypoglycemic symptoms |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- The recruited subjects will reflect the gender and ethnic distribution of the Yale and New Haven community. The recruited subjects with type 1 diabetes will reflect the demographics of the clinic population in New Haven. Subject selection is independent of race and sex.
Key inclusion criteria (8 listed)
- All subjects:
- on a weight maintaining diet
- ability to read and speak English fluently
- For All Type 1 Diabetics all of the above inclusion criteria AND C-peptide negative AND no evidence of neuropathy or proliferative retinopathy
- Only for Type 1 Diabetics in the intensively treated group: HbA1c < 7.5% AND documented hypoglycemia at least once per week over at least 4 weeks of frequent daily self monitoring
Key exclusion criteria (2 listed)
- Pregnancy
- History of neurologic or cardiovascular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Brain response to blood glucose levels
Time frame: 4 to 8 weeks
Brain response is operationally defined as: fMRI BOLD signal to detect differences in brain activation in response to changes in glucose levels taken between 4 to 8 weeks after subject enrollment.
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 18 Apr 2022.
- Derived from this study: PubMed 31511876Parikh L, Seo D, Lacadie C, Belfort-Deaguiar R, Groskreutz D, Hamza M, Dai F, Scheinost D, Sinha R, Todd Constable R, Sherwin R, Hwang JJ. Differential Resting State Connectivity Responses to Glycemic State in Type 1 Diabetes. J Clin Endocrinol Metab. 2020 Jan 1;105(1):1-13. doi: 10.1210/clinem/dgz004.
Related trials for Type 1 Diabetes
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
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.
Robert Sherwin, M.D. principal investigator
Yale University
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 Type 1 Diabetes and Hypoglycemia, run by Yale University 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 8 inclusion and 2 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 18 Apr 2022. 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?
Brain response to blood glucose levels (time frame: 4 to 8 weeks). 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 NCT00580710, 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 18 Apr 2022.