Diabetes Mellitus, Type 1NCT02772783
Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus
A study testing high GI meal, low GI meal and euglycemic insulin clamp in people with Diabetes Mellitus, Type 1, run by Boston Children's Hospital at 1 site in United States.
Trial summary
Processed carbohydrates cause rapid changes in blood sugar and have been associated with overeating and obesity. We have shown that test meals high in processed carbohydrate affect brain areas involved in addiction, craving and overeating. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men only
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- high GI meal, low GI meal and euglycemic insulin clamp
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to May 2018
- Phase
- Interventional
- 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 45 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Type 1 diabetes for a minimum of 3 years
- BMI 20-35 kg/m2
- Use of insulin pump
- Willing and able to: Maintain weight and document for duration of the study
Who cannot join
- Insulin resistance (current insulin requirement > 1.5 U/kg/d)
- Insulin requirement < 0.5 unit/kg/day (cut-off for preserved beta-cell function)
- HbA1C ≥ 8.0%
- DKA within 2 months
- Frequent hypoglycemia (BG <50 mg/dl), > 3 times per week
- Fluctuations in body weight >10% over preceding year
Show all 13Show fewer
- Smoking or illicit substance abuse
- High levels of physical activity (≥60 minutes per day, ≥ 4 days per week)
- Current weight loss diet
- Medical problems, medications or dietary supplements that may affect metabolism, insulin action, body weight, appetite, energy expenditure, or gastrointestinal absorption (e.g. celiac disease)
- Allergies to compounds or intolerance of the liquid meals
- MRI exclusion criteria
- Other conditions according to self-report that would prohibit participation based and researcher assessment
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
About this study
Processed carbohydrates cause rapid changes in blood sugar and have been associated with overeating and obesity. We have shown that test meals high in processed carbohydrate affect brain areas involved in addiction, craving and overeating. It is unknown whether the changes in blood sugar or the associated higher insulin levels mediate this brain activation and its likely adverse effects.
Answering this question is important for patients with type 1 diabetes who have elevated risks of obesity and disordered eating: If blood sugar is the causal mechanism, optimal insulin coverage should be protective. If insulin is the causal mechanism, however, a diet high in processed carbohydrate could predispose to overeating and weight gain, as this diet requires higher insulin doses.
To disentangle these factors, we will study brain activation and relevant blood markers in 15 men with diabetes. In 4 sessions, we will examine meals with differential carbohydrate properties while giving insulin infusions.
Read the detailed description
A total of 15 male participants (age 18-45) with T1DM will be recruited. Participants will be enrolled in the study for a total of 1-3 months, and participate in a pre-test visit and three test visits, each after a 10-12-hr overnight fast. Participants will be instructed to consume their regular, weight maintaining diet between visits.
At the pre-test visit, the study director or PI will meet participants, confirm eligibility and obtain informed consent. Participants will receive a low glycemic index (GI) meal with optimal iv insulin coverage using a negative feedback algorithm to maintain euglycemia (euglycemic clamp). Insulin requirement will be quantified. At some time during the visit, participants will present to the BIDMC research imaging facility for a practice MRI session, during which they will undergo a brief imaging sequence to get accustomed to the scanning process and eliminate anxiety as a confounder of imaging data.
At each of 3 test visits, one of the following experimental conditions will be applied in a randomized, blinded cross-over design: (a) high GI meal with euglycemic clamp, (b) low GI meal with euglycemic clamp, (c) high GI meal with primed-variable insulin infusion at the rate established during the pre-test visit. After steady state is established, baseline laboratory evaluation and MRI imaging will be obtained, followed by the test meal. Imaging will be repeated at 1 and 4 hours postprandial. Blood samples for pertinent metabolic and hormonal parameters will be obtained every 30 minutes. Each test-visit concludes with a standard weighed meal to quantify ad-libitum intake.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- high GI meal, low GI meal, euglycemic insulin clamp, primed-variable insulin infusion
- Keywords
- brain, fMRI, carbohydrate, insulin clamp, intake regulation, overweight, glycemic index
- Medical subject headings
- Diabetes Mellitus, Type 1, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
high GI mealOther
High and low GI liquid test meals are matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals will provide 25% of individual daily energy requirements as estimated by the Harris Benedict equation. A high glycemic index of ~90 is achieved by using corn syrup as a carbohydrate source.
low GI mealOther
High and low GI liquid test meals are matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals will provide 25% of individual daily energy requirements as estimated by the Harris Benedict equation. A low glycemic index of ~40 is achieved by using uncooked corn starch as a carbohydrate source.
euglycemic insulin clampDrug
Insulin will be given intravenously for 5 hours. During the entire clamp protocol, glucose levels will be measured every 5 minutes. A basal insulin infusion will be started at 80% of the patients insulin pump basal rate, and will be adjusted between 0.1 and 2.5 mU/kg•min, depending upon the patient's plasma glucose level in relation to the target range target of 90-100 mg/dl.
primed-variable insulin infusionDrug
A primed-variable infusion of insulin will be administered at the rate established to achieve euglycemia after a low glycemic index meal. This is expected to result in moderate hyperglycemia as the high GI meal is associated with higher insulin requirements. For patient safety, glucose levels will be measured every 30 minutes. If glucose levels are > 400 mg/dl or < 60 mg/dl, insulin infusion will be adjusted to maintain glucose levels target of 60-400 mg/dl.
| Study group | Role | What they receive |
|---|---|---|
| high GI meal, euglycemic insulin clamp | Experimental | A nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia.This condition results in euglycemia with high insulin levels. Receives: Other: high GI meal; Drug: euglycemic insulin clamp |
| high GI meal, fixed insulin infusion | Experimental | A nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously at a rate previously established to maintain euglycemia after a low glycemic index meal. This condition results in moderate hyperglycemia with low insulin levels. Receives: Other: high GI meal; Drug: primed-variable insulin infusion |
| low GI meal, euglycemic insulin clamp | Active comparator | A nutritional shake with low GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia. This condition results in euglycemia with low insulin levels. Receives: Other: low GI meal; Drug: euglycemic insulin clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nucleus Accumbens Blood Flow
Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.
Measured: 4 hrs postprandial
Secondary outcomes (5)
Nucleus Accumbens Blood Flow
Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.
Measured: 1 hr postprandial
Blood Flow in Other Brain Areas Involved in Intake Regulation - Dorsal Caudate
Cerebral blood flow was measured by arterial spin labeling (MRI). Grouped MRI data was visually inspected for postprandial differences between conditions. Blood flow from a cluster contracting the conditions in the right dorsal caudate, just lateral to the nucleus accumbent, was extracted, normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.
Measured: 4 hrs postprandial
Blood Flow in Other Brain Areas Involved in Intake Regulation - Ventrolateral Striatum
Cerebral blood flow was measured by arterial spin labeling (MRI). Grouped MRI data was visually inspected for postprandial differences between conditions. Blood flow from a cluster contracting the conditions in the right ventrolateral striatum, just lateral to the nucleus accumbent, was extracted, normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.
Measured: 1 hr postprandial
Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation
Cerebral blood oxygen concentration level was measured by resting state functional MRI (rs-fMRI). Seed based analysis was performed with the seed on the right Nucleus Accumbens. Functional connectivity between Nucleus Accumbens and Hypothalamus was assessed through extraction of temporal correlation measures.
Measured: 4 hrs postprandial
Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation
Cerebral blood oxygen concentration level was measured by resting state functional MRI (rs-fMRI). Seed based analysis was performed with the seed on the right Nucleus Accumbens. Functional connectivity between Nucleus Accumbens and Hypothalamus was assessed through extraction of temporal correlation measures. Functional connectivity between Nucleus Accumbens and other brain areas was visually assessed.
Measured: 1 hr postprandial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2016 (estimated)
- Study startJul 2016
- Primary completionMay 2018
- Study completionMay 2018
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.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Belinda Lennerz, Boston Children's Hospital
- Investigators
- Belinda S Lennerz, MD, PhD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02772783
- Sponsor's protocol ID
- IRB-P00022176
- Other IDs
- IRB- 2016P000079
- Status last verified
- May 2021
- First submitted
- 11 May 2016
- Last updated
- 18 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT02772783
- Acronym / sponsor ID
- IRB-P00022176
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- brain, fMRI, carbohydrate, insulin clamp, intake regulation, overweight, glycemic index
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Brigham and Women's Hospital
- Study start
- Jul 2016
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 16 May 2016 (estimated)
- Results
- Posted 18 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Processed carbohydrates cause rapid changes in blood sugar and have been associated with overeating and obesity. We have shown that test meals high in processed carbohydrate affect brain areas involved in addiction, craving and overeating. It is unknown whether the changes in blood sugar or the associated higher insulin levels mediate this brain activation and its likely adverse effects.
Answering this question is important for patients with type 1 diabetes who have elevated risks of obesity and disordered eating: If blood sugar is the causal mechanism, optimal insulin coverage should be protective. If insulin is the causal mechanism, however, a diet high in processed carbohydrate could predispose to overeating and weight gain, as this diet requires higher insulin doses.
To disentangle these factors, we will study brain activation and relevant blood markers in 15 men with diabetes. In 4 sessions, we will examine meals with differential carbohydrate properties while giving insulin infusions.
Detailed description
A total of 15 male participants (age 18-45) with T1DM will be recruited. Participants will be enrolled in the study for a total of 1-3 months, and participate in a pre-test visit and three test visits, each after a 10-12-hr overnight fast. Participants will be instructed to consume their regular, weight maintaining diet between visits.
At the pre-test visit, the study director or PI will meet participants, confirm eligibility and obtain informed consent. Participants will receive a low glycemic index (GI) meal with optimal iv insulin coverage using a negative feedback algorithm to maintain euglycemia (euglycemic clamp). Insulin requirement will be quantified. At some time during the visit, participants will present to the BIDMC research imaging facility for a practice MRI session, during which they will undergo a brief imaging sequence to get accustomed to the scanning process and eliminate anxiety as a confounder of imaging data.
At each of 3 test visits, one of the following experimental conditions will be applied in a randomized, blinded cross-over design: (a) high GI meal with euglycemic clamp, (b) low GI meal with euglycemic clamp, (c) high GI meal with primed-variable insulin infusion at the rate established during the pre-test visit. After steady state is established, baseline laboratory evaluation and MRI imaging will be obtained, followed by the test meal. Imaging will be repeated at 1 and 4 hours postprandial. Blood samples for pertinent metabolic and hormonal parameters will be obtained every 30 minutes. Each test-visit concludes with a standard weighed meal to quantify ad-libitum intake.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| high GI meal, euglycemic insulin clamp | Experimental | Other: high GI meal, Drug: euglycemic insulin clampA nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia.This condition results in euglycemia with high insulin levels. |
| high GI meal, fixed insulin infusion | Experimental | Other: high GI meal, Drug: primed-variable insulin infusionA nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously at a rate previously established to maintain euglycemia after a low glycemic index meal. This condition results in moderate hyperglycemia with low insulin levels. |
| low GI meal, euglycemic insulin clamp | Active comparator | Other: low GI meal, Drug: euglycemic insulin clampA nutritional shake with low GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia. This condition results in euglycemia with low insulin levels. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Type 1 diabetes for a minimum of 3 years
- BMI 20-35 kg/m2
- Use of insulin pump
- Willing and able to: Maintain weight and document for duration of the study
Key exclusion criteria (13 listed)
- Insulin resistance (current insulin requirement > 1.5 U/kg/d)
- Insulin requirement < 0.5 unit/kg/day (cut-off for preserved beta-cell function)
- HbA1C ≥ 8.0%
- DKA within 2 months
- Frequent hypoglycemia (BG <50 mg/dl), > 3 times per week
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 |
|---|---|---|
| high GI mealHigh and low GI liquid test meals are matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals will provide 25% of individual daily energy requirements as estimated by the Harris Benedict equation. A high glycemic index of ~90 is achieved by using corn syrup as a carbohydrate source. | Other | high GI meal, euglycemic insulin clamp, high GI meal, fixed insulin infusion |
| low GI mealHigh and low GI liquid test meals are matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals will provide 25% of individual daily energy requirements as estimated by the Harris Benedict equation. A low glycemic index of ~40 is achieved by using uncooked corn starch as a carbohydrate source. | Other | low GI meal, euglycemic insulin clamp |
| euglycemic insulin clampInsulin will be given intravenously for 5 hours. During the entire clamp protocol, glucose levels will be measured every 5 minutes. A basal insulin infusion will be started at 80% of the patients insulin pump basal rate, and will be adjusted between 0.1 and 2.5 mU/kg•min, depending upon the patient's plasma glucose level in relation to the target range target of 90-100 mg/dl. | Drug | high GI meal, euglycemic insulin clamp, low GI meal, euglycemic insulin clamp |
| primed-variable insulin infusionA primed-variable infusion of insulin will be administered at the rate established to achieve euglycemia after a low glycemic index meal. This is expected to result in moderate hyperglycemia as the high GI meal is associated with higher insulin requirements. For patient safety, glucose levels will be measured every 30 minutes. If glucose levels are > 400 mg/dl or < 60 mg/dl, insulin infusion will be adjusted to maintain glucose levels target of 60-400 mg/dl. | Drug | high GI meal, fixed insulin infusion |
Primary outcome
Nucleus Accumbens Blood Flow
Time frame: 4 hrs postprandial
Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan.
5 secondary outcomes
Nucleus Accumbens Blood Flow
Time frame: 1 hr postprandial
Blood Flow in Other Brain Areas Involved in Intake Regulation - Dorsal Caudate
Time frame: 4 hrs postprandial
Blood Flow in Other Brain Areas Involved in Intake Regulation - Ventrolateral Striatum
Time frame: 1 hr postprandial
Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation
Time frame: 4 hrs postprandial
Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation
Time frame: 1 hr postprandial
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Diabetes Mellitus, Type 1
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.
Belinda S Lennerz, MD, PhD principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing high GI meal, low GI meal and euglycemic insulin clamp in people with Diabetes Mellitus, Type 1, run by Boston Children's Hospital 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 13 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 Jun 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 18 Jun 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?
Nucleus Accumbens Blood Flow (time frame: 4 hrs postprandial). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jun 2021.