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NCT Number: NCT03710928

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

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.

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Key information

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location status: Recruiting

Location contact

Belinda S Lennerz, MD PhD

CONTACT

[email protected]

8572183896

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • Standard MRI exclusion criteria
  • Irregular menses
  • 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)

Treatment and study plan

Very low carbohydrate diet

Other

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

Other

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.

Primary outcomes

  1. Hemoglobin A1C change

    Time frame: 12 weeks - baseline

    HbA1C change from baseline at 12 weeks will be compared between the 2 interventions

Secondary outcomes

  1. total daily insulin dose

    Time frame: week 0 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 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 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 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 and 12

    will be calculated from 1-week continuous glucose monitoring data

  6. percent time spent in hyperglycemia

    Time frame: week 0 and 12

    will be calculated from 1-week continuous glucose monitoring data

  7. blood glucose average

    Time frame: week 0 and 12

    will be calculated from 1-week continuous glucose monitoring data

  8. blood glucose standard deviation

    Time frame: week 0 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 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 and 12

    will be calculated by dividing blood glucose standard deviation by blood glucose average

  11. fasting total cholesterol

    Time frame: week 0 and 12

    from venous blood

  12. fasting high density lipoprotein cholesterol

    Time frame: week 0 and 12

    from venous blood

  13. fasting low density lipoprotein cholesterol

    Time frame: week 0 and 12

    from venous blood

  14. fasting triglycerides

    Time frame: week 0 and 12

    from venous blood

  15. fasting beta hydroxybutyrate

    Time frame: weeks 0, 1, 2, 4, 6, 9, 12

    from venous blood and/or point-of-care testing

  16. fasting high-sensitivity c-reactive protein

    Time frame: week 0 and 12

    from venous blood

  17. 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.

  18. Becks Depression Inventory II (BDI II) less suicidality

    Time frame: week 0, 6, and 12

    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.

  19. 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.

  20. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Azova

CONTACT

Belinda Lennerz, MD PhD

CONTACT

[email protected]

8572183896

Sponsors and collaborators

Lead sponsor

Boston Children's Hospital

Other

Registry information

Important dates

Study start
2020
Primary completion
2026
Study completion
2026
First posted
Oct 18, 2018
Registry last updated
Dec 18, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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