Type 1 Diabetes Management Using a Very Low Carbohydrate Versus Standard Diet

• ClinicalTrials.gov Identifier: NCT03710928
• Recruitment Status: Recruiting
• First Posted: October 18, 2018
• Last Update Posted: February 10, 2021
• Sponsor: Boston Children's Hospital
• Information provided by (Responsible Party): Belinda Lennerz, Boston Children's Hospital

Study Description

Brief Summary:

Despite major technological advances, management of type one diabetes mellitus (T1D) remains suboptimal, putting millions of people at risk for immediate and long-term complications. After meals, a mismatch between carbohydrate absorption rate and insulin action typically leads to alternating periods of hyper- and hypoglycemia. A conceptually promising approach to control both problems is dietary carbohydrate restriction to reduce postprandial blood glucose changes and insulin needs. In a prior survey study, the investigators documented exceptional glycemic control (HbA1c 5.67%) and low acute complication rates among 316 children and adults with T1D consuming a very-low-carbohydrate diet.

To test the feasibility of this approach, the investigators will conduct a randomized-controlled feeding study involving 32 adults and adolescents with T1D. Participants will be randomized to receive a very low carbohydrate vs. standard carbohydrate diet. Participants will be in the study for 12 weeks and receive all their meals by meal delivery.They will share continuous glucose monitoring data with the study team and be in close communication to adjust insulin doses as needed. All participants will have a screening visit, an individual or group education session, and 7 study visits with fasting blood draws to evaluate diabetes control and metabolic health. Two of the visits will also comprise additional metabolic studies to assess glucagon response and brain function during hypoglycemia by magnetic resonance imaging (MRI). Participants will have IV catheters placed and receive IV insulin to drop blood glucose levels to 50 mg/dl for up to 30 minutes. The primary outcome will be HbA1C change from baseline. Secondary outcomes include detailed measures of glycemic variability, metabolic health, and quality of life.

Condition or disease	Intervention/treatment	Phase
Type1diabetes	Other: very low carbohydrate diet; Other: standard carbohydrate diet	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomized controlled trial, 12-week feeding study
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Type 1 Diabetes Management Using a Very Low Carbohydrate Versus Standard Diet
• Actual Study Start Date: January 3, 2020
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: very low carbohydrate diet; Dietary Intervention, food delivery	Other: very low carbohydrate diet; All meals will be delivered and participants will consume study foods exclusively. Participants will receive a fiber supplement as needed with each meal to support digestive health, and a daily multi-vitamin, magnesium and omega-three supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance. The diet composition will be as follows: 5% carbohydrate, 70% fat, 20% protein.
Active Comparator: standard diet; Dietary Intervention, food delivery	Other: standard carbohydrate diet; All meals will be delivered and participants will consume study foods exclusively. Participants will receive a daily multi-vitamin and omega-3 supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance. The diet composition will be as follows: 50% carbohydrate, 30% fat, 20% protein.

Outcome Measures

Primary Outcome Measures :

1. Hemoglobin A1C change [ Time Frame: 12 weeks - baseline ]
   HbA1C change from baseline at 12 weeks will be compared between the 2 interventions

Secondary Outcome Measures :

1. total daily insulin dose [ Time Frame: week 0, 6 and 12 ]
   average daily insulin dose over 1 week will be calculated
2. percent time spent in the glycemic target range of 70-140 mg/dl [ Time Frame: week 0, 6 and 12 ]
   will be calculated from 1-week continuous glucose monitoring data
3. percent time spent below the glycemic target of 70 mg/dl [ Time Frame: week 0, 6 and 12 ]
   will be calculated from 1-week continuous glucose monitoring data
4. percent time in hypoglycemia below 54 mg/dl [ Time Frame: week 0, 6 and 12 ]
   will be calculated from 1-week continuous glucose monitoring data
5. percent time spent above the glycemic target of 140 mg/dl [ Time Frame: week 0, 6 and 12 ]
   will be calculated from 1-week continuous glucose monitoring data
6. percent time spent in hyperglycemia [ Time Frame: week 0, 6 and 12 ]
   will be calculated from 1-week continuous glucose monitoring data
7. blood glucose average [ Time Frame: week 0, 6 and 12 ]
   will be calculated from 1-week continuous glucose monitoring data
8. blood glucose standard deviation [ Time Frame: week 0, 6 and 12 ]
   will be calculated from 1-week continuous glucose monitoring data
9. Glycemic Variability Index, a measure for glycemic variability normalized to mean blood glucose level [ Time Frame: week 0, 6 and 12 ]
   will be calculated by dividing blood glucose standard deviation by blood glucose average
10. Mean Amplitude of Glycemic Excursions (MAGE), a measure for postprandial glycemic variability [ Time Frame: week 0, 6 and 12 ]
    will be calculated by dividing blood glucose standard deviation by blood glucose average
11. fasting total cholesterol [ Time Frame: week 0, 6 and 12 ]
    from venous blood
12. fasting high density lipoprotein cholesterol [ Time Frame: week 0, 6 and 12 ]
    from venous blood
13. fasting low density lipoprotein cholesterol [ Time Frame: week 0, 6 and 12 ]
    from venous blood
14. fasting triglycerides [ Time Frame: week 0, 6 and 12 ]
    from venous blood
15. fasting beta hydroxybutyrate [ Time Frame: weeks 0, 1, 2, 4, 6, 9, 12 ]
    from venous blood
16. fasting bicarbonate [ Time Frame: weeks 0, 1, 2, 4, 6, 9, 12 ]
    from venous blood
17. fasting high-sensitivity c-reactive protein [ Time Frame: week 0, 6 and 12 ]
    from venous blood
18. Self-reported quality of life assessed per self-report by The Problem Areas in Diabetes Scale (PAID) [ Time Frame: week 0, 6 and 12 ]
    The scores for each item are summed, then multiplied by 1.25 to generate a total score out of 100.
19. Becks Depression Inventory II (BDI II) [ Time Frame: week 0, 6 and 12 ]
    BDI-II is a 21-item self-report inventory that measures assesses for presence and severity of depression depressive symptoms. Each item is scored between 0-3. Item scores are added up to a total score (max. 63) and reported.
20. Yale Food Addiction Scale 2.0 (YFAS 2.0) [ Time Frame: week 0, 6 and 12 ]
    Assesses indicators of addictive-like eating.The YFAS includes two scoring options: 1) a "symptom count" that reflects the number of addiction-like criteria endorsed and 2) a dichotomous "diagnosis" that indicates whether a threshold of three or more "symptoms" plus clinically significant impairment or distress has been met. The diagnosis score will be calculated at baseline and used as an effect modifier. Symptom counts will be reported separately as a longitudinal measure.
21. Highly Processed Food Withdrawal Scale (ProWS) [ Time Frame: Baseline, daily on days 1-7, then weekly; primary focus on change from baseline to day 7 ]
    Assesses withdrawal-type symptoms that may occur when individuals cut down on rewarding foods.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 30 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males and females with T1D for at least 1 year
• Age 18 to 30 years
• Tanner stage ≥ IV
• BMI 18.5-30 kg/m2
• Stable glycemic control (HbA1c 7-9%)
• Use of a continuous glucose monitor (CGM)
• Use of an insulin pump
• Attendance of at least 3 diabetes care visits over the past 12 months

Exclusion Criteria:

• Ketoacidosis or severe hypoglycemia with seizure or coma in the past year
• Dietary restrictions or intolerances that are incompatible with the planned food deliveries, e.g. celiac disease, gastroparesis, certain food allergies
• Following a weight-loss or otherwise restrictive diet
• Use of medications or supplements other than insulin to control blood glucose
• Vigorous exercise >2 hours on >3 days a week
• History of an eating disorder or at risk for eating disorder, assessed by the Eating Disorders Diagnostic Scale (EDDS)
• Major medical illness or use of medications that could interfere with metabolic or glycemic variables
• Significant psychiatric illness or use of psychotropic medication
• Smoking, use of recreational drugs, or excessive alcohol consumption
• Pregnancy or breastfeeding
• Irregular menses
• Standard MRI exclusion criteria

Contacts and Locations

Contacts

Contact: Belinda Lennerz, MD PhD; 8572183896; belinda.lennerz@childrens.harvard.edu

Contact: Svetlana Azova, MD; 6173557476; svetlana.azova@childrens.harvard.edu

Locations

United States, Massachusetts

Boston Children's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Belinda S Lennerz, MD PhD 857-218-3896 belinda.lennerz@childrens.harvard.edu

Contact: Svetlana C Azova, MD 6179196675 svetlana.azova@childrens.harvard.edu

Boston Children's Hospital; Not yet recruiting

Boston, Massachusetts, United States, 02446

Contact: Belinda Lennerz, MD PhD 857-218-3896 ext 6173557476 belinda.lennerz@childrens.harvard.edu

Contact: David Ludwig 617 355 4878 ext 6173557476 david.ludwig@childrens.harvard.edu

Sub-Investigator: David Ludwig, MD PhD

Principal Investigator: Belinda Lennerz

Sub-Investigator: Svetlana Azova

Sponsors and Collaborators

Boston Children's Hospital

More Information

Publications:

Lennerz BS, Barton A, Bernstein RK, Dikeman RD, Diulus C, Hallberg S, Rhodes ET, Ebbeling CB, Westman EC, Yancy WS Jr, Ludwig DS. Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet. Pediatrics. 2018 Jun;141(6). pii: e20173349. doi: 10.1542/peds.2017-3349. Epub 2018 May 7.

• Responsible Party: Belinda Lennerz, Principal Investigator, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT03710928
• Other Study ID Numbers: IRB-P00030039
• First Posted: October 18, 2018
• Last Update Posted: February 10, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Belinda Lennerz, Boston Children's Hospital:

very low carbohydrate diet; nutrition; ketogenic diet; ketosis; nutritional ketosis; metabolism; metabolic health

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases