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Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02772783
Recruitment Status : Completed
First Posted : May 16, 2016
Last Update Posted : May 8, 2018
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Information provided by (Responsible Party):
Belinda Lennerz, Boston Children’s Hospital

Tracking Information
First Submitted Date  ICMJE May 11, 2016
First Posted Date  ICMJE May 16, 2016
Last Update Posted Date May 8, 2018
Study Start Date  ICMJE July 2016
Actual Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2016)
Nucleus Accumbens blood flow (right and left) [ Time Frame: 4 hrs postprandial ]
by arterial spin labeling (MRI)
Original Primary Outcome Measures  ICMJE
 (submitted: May 11, 2016)
Nucleus Accumbens blood flow [ Time Frame: 4 hrs postprandial ]
by arterial spin labeling (MRI)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2016)
  • Nucleus Accumbens blood flow [ Time Frame: 1 hr postprandial ]
    by arterial spin labeling (ASL) MRI
  • blood flow in other brain areas involved in intake regulation [ Time Frame: 4 hrs postprandial ]
    by ASL
  • blood flow in other brain areas involved in intake regulation [ Time Frame: 1 hr postprandial ]
    by ASL
  • functional connectivity of Nucleus Accumbens, Hypothalamus and other brain areas involved in intake regulation [ Time Frame: 4 hrs postprandial ]
    by resting state functional MRI (rs-fMRI)
  • functional connectivity of Nucleus Accumbens, Hypothalamus and other brain areas involved in intake regulation [ Time Frame: 1 hr postprandial ]
    by rs-fMRI
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 11, 2016)
  • plasma glucose level [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes
  • serum insulin level [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes
  • serum fatty acids [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes
  • plasma ghrelin [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel
  • plasma GLP-1 [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel
  • plasma PYY [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel
  • plasma CCK [ Time Frame: 0-4.5 hrs postprandial ]
    analyzed as part of a metabolic hormone panel
  • plasma glucagon [ Time Frame: 0-4.5 hrs postprandial ]
    blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel
  • plasma leptin [ Time Frame: 0-4.5 hrs postprandial ]
    analyzed as part of a metabolic hormone panel
  • metabolomics [ Time Frame: 0, 1 and 4 hrs postprandial ]
    LC-MS/MS methodology using several chromatographic stationary phases for > 400 metabolites
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus
Official Title  ICMJE Dietary Glycemic Index, Brain Function and Food Intake in Patients With Type 1 Diabetes Mellitus
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 1
Intervention  ICMJE
  • Other: high GI meal
    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.
  • Other: low GI meal
    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.
  • Drug: euglycemic insulin clamp
    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.
  • Drug: primed-variable insulin infusion
    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 Arms  ICMJE
  • Experimental: high GI meal, euglycemic insulin clamp
    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.
    Interventions:
    • Other: high GI meal
    • Drug: euglycemic insulin clamp
  • Experimental: high GI meal, fixed insulin infusion
    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.
    Interventions:
    • Other: high GI meal
    • Drug: primed-variable insulin infusion
  • Active Comparator: low GI meal, euglycemic insulin clamp
    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.
    Interventions:
    • Other: low GI meal
    • Drug: euglycemic insulin clamp
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 11, 2016)
15
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2018
Actual Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02772783
Other Study ID Numbers  ICMJE IRB-P00022176
IRB- 2016P000079 ( Other Identifier: Beth Israel Deaconess Medical Center )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Belinda Lennerz, Boston Children’s Hospital
Study Sponsor  ICMJE Boston Children’s Hospital
Collaborators  ICMJE
  • Beth Israel Deaconess Medical Center
  • Brigham and Women's Hospital
Investigators  ICMJE
Principal Investigator: Belinda S Lennerz, MD, PhD Boston Children’s Hospital
PRS Account Boston Children’s Hospital
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP