Clinical trial NCT03710928: Type 1 Diabetes Management Using a Very Low Carbohydrate Versus Standard Diet
Official title: Type 1 Diabetes Management Using a Very Low Carbohydrate Versus Standard Diet
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type1diabetes
Keywords: very low carbohydrate diet
nutrition
ketogenic diet
ketosis
nutritional ketosis
metabolism
metabolic health
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2018-10-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled trial, 12-week feeding study
Primary purpose: SUPPORTIVE_CARE

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 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Hemoglobin A1C change
timeFrame: 12 weeks - baseline
Secondary outcomes:
measure: total daily insulin dose
timeFrame: week 0 and 12
measure: percent time spent in the glycemic target range of 70-140 mg/dl
timeFrame: week 0 and 12
measure: percent time spent below the glycemic target of 70 mg/dl
timeFrame: week 0 and 12
measure: percent time in hypoglycemia below 54 mg/dl
timeFrame: week 0 and 12
measure: percent time spent above the glycemic target of 140 mg/dl
timeFrame: week 0 and 12
measure: percent time spent in hyperglycemia
timeFrame: week 0 and 12
measure: blood glucose average
timeFrame: week 0 and 12
measure: blood glucose standard deviation
timeFrame: week 0 and 12
measure: Glycemic Variability Index, a measure for glycemic variability normalized to mean blood glucose level
timeFrame: week 0 and 12
measure: Mean Amplitude of Glycemic Excursions (MAGE), a measure for postprandial glycemic variability
timeFrame: week 0 and 12
measure: fasting total cholesterol
timeFrame: week 0 and 12
measure: fasting high density lipoprotein cholesterol
timeFrame: week 0 and 12
measure: fasting low density lipoprotein cholesterol
timeFrame: week 0 and 12
measure: fasting triglycerides
timeFrame: week 0 and 12
measure: fasting beta hydroxybutyrate
timeFrame: weeks 0, 1, 2, 4, 6, 9, 12
measure: fasting high-sensitivity c-reactive protein
timeFrame: week 0 and 12
measure: Self-reported quality of life assessed per self-report by The Problem Areas in Diabetes Scale (PAID)
timeFrame: week 0, 6, and 12
measure: Becks Depression Inventory II (BDI II) less suicidality
timeFrame: week 0, 6, and 12
measure: Yale Food Addiction Scale 2.0 (YFAS 2.0)
timeFrame: week 0, 6, and 12
measure: Highly Processed Food Withdrawal Scale (ProWS)
timeFrame: Baseline, daily on days 1-7, then weekly; primary focus on change from baseline to day 7
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
References:
citation: 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.