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

Type1diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03710928
• Other study ID #: IRB-P00030039
• Status: Recruiting
• Phase: N/A
• Start date: January 3, 2020
• Est. completion date: July 31, 2024

Study information

• Verified date: June 2023
• Source: Boston Children's Hospital
• Contact: Belinda Lennerz, MD PhD
• Phone: 8572183896
• Email: belinda.lennerz[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 3 study visits to evaluate diabetes control and metabolic health. Some of these visits will have a fasting blood draw. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Males and females with T1D for at least 1 year

• Age 18 to 40 years

• Tanner stage = IV

• BMI 18.5-35 kg/m2

• Stable glycemic control (HbA1c 6.5-9%)

• Use of a continuous glucose monitor (CGM)

• Use of an insulin pump

• Attendance of at least 1 diabetes care visit over the past 12 months (including virtual)

Exclusion Criteria:

• Ketoacidosis or severe hypoglycemia with seizure or coma in the past 6 months

• 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

• 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 other than insulin and metformin that could interfere with metabolic or glycemic variables

• Significant psychiatric illness

• Smoking, use of recreational drugs, or excessive alcohol consumption

• Pregnancy or breastfeeding

• Anemia

• For participants who undergo MRI:

1. Standard MRI exclusion criteria

2. Irregular menses

3. Use of psychotropic medication other than SSRIs or other mild antidepressant or anxiety medications (unless these medications are safe to be held for several days to allow for the acquisition of MRI data)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type1diabetes

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boston Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

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):e20173349. doi: 10.1542/peds.2017-3349. Epub 2018 May 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemoglobin A1C change	HbA1C change from baseline at 12 weeks will be compared between the 2 interventions	12 weeks - baseline
Secondary	total daily insulin dose	average daily insulin dose over 1 week will be calculated	week 0 and 12
Secondary	percent time spent in the glycemic target range of 70-140 mg/dl	will be calculated from 1-week continuous glucose monitoring data	week 0 and 12
Secondary	percent time spent below the glycemic target of 70 mg/dl	will be calculated from 1-week continuous glucose monitoring data	week 0 and 12
Secondary	percent time in hypoglycemia below 54 mg/dl	will be calculated from 1-week continuous glucose monitoring data	week 0 and 12
Secondary	percent time spent above the glycemic target of 140 mg/dl	will be calculated from 1-week continuous glucose monitoring data	week 0 and 12
Secondary	percent time spent in hyperglycemia	will be calculated from 1-week continuous glucose monitoring data	week 0 and 12
Secondary	blood glucose average	will be calculated from 1-week continuous glucose monitoring data	week 0 and 12
Secondary	blood glucose standard deviation	will be calculated from 1-week continuous glucose monitoring data	week 0 and 12
Secondary	Glycemic Variability Index, a measure for glycemic variability normalized to mean blood glucose level	will be calculated by dividing blood glucose standard deviation by blood glucose average	week 0 and 12
Secondary	Mean Amplitude of Glycemic Excursions (MAGE), a measure for postprandial glycemic variability	will be calculated by dividing blood glucose standard deviation by blood glucose average	week 0 and 12
Secondary	fasting total cholesterol	from venous blood	week 0 and 12
Secondary	fasting high density lipoprotein cholesterol	from venous blood	week 0 and 12
Secondary	fasting low density lipoprotein cholesterol	from venous blood	week 0 and 12
Secondary	fasting triglycerides	from venous blood	week 0 and 12
Secondary	fasting beta hydroxybutyrate	from venous blood and/or point-of-care testing	weeks 0, 1, 2, 4, 6, 9, 12
Secondary	fasting high-sensitivity c-reactive protein	from venous blood	week 0 and 12
Secondary	Self-reported quality of life assessed per self-report by The Problem Areas in Diabetes Scale (PAID)	The scores for each item are summed, then multiplied by 1.25 to generate a total score out of 100.	week 0, 6, and 12
Secondary	Becks Depression Inventory II (BDI II) less suicidality	BDI-II less suicidality is a 20-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. 60) and reported.	week 0, 6, and 12
Secondary	Yale Food Addiction Scale 2.0 (YFAS 2.0)	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.	week 0, 6, and 12
Secondary	Highly Processed Food Withdrawal Scale (ProWS)	Assesses withdrawal-type symptoms that may occur when individuals cut down on rewarding foods.	Baseline, daily on days 1-7, then weekly; primary focus on change from baseline to day 7