Clinical trial NCT03652649: Treatment of Type 2 Diabetes With Ketogenic Diet
Official title: Evaluation of Efficacy and Safety of Ketogenic Complete Meal Replacement as Treatment of Obesity-related Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Type2 Diabetes Mellitus
Obesity
Keywords: type 2 diabetes
diabetes
ketogenic diet
low carb diet
weight loss
obesity
diet treatment
nutrition
BMI
Lead sponsor: Mid-Atlantic Epilepsy and Sleep Center, LLC
Sponsor class: OTHER
First posted: 2018-08-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy and safety of ketogenic diet (KD) complete meal replacement treatment of obesity-related Type 2 diabetes mellitus (T2DM) and of obesity in patients with obesity and T2DM. This will be an open-label single arm study evaluating glycemic control and weight loss in obese participants with type 2 diabetes treated for 6 months with 3:1 \[fat\]:\[protein+carbohydrate\] ratio, 1600 kcal/day diet.

Detailed description: The purpose of the study is to evaluate the efficacy and safety of ketogenic diet (KD) complete meal replacement treatment of obesity-related Type 2 diabetes mellitus (T2DM) and of obesity in patients with obesity and T2DM. This will be an open-label single arm study evaluating glycemic control and weight loss in obese participants with type 2 diabetes treated for 6 months with 3:1 \[fat\]:\[protein+carbohydrate\] ratio, 1600 kcal/day diet.

Treatment will consist of KD complete meal replacement with 3:1 \[fat\]: \[protein + carbohydrate\] weight ratio, and with 1600 kcal restriction. It will consist of pre-made meals, including breakfast, lunch, dinner and two snacks, one each between breakfast and lunch and lunch and dinner. Meals will be made according to supplied recipes (Anemone, LLC.) with a 3-week long meal plan consisting of different recipes for the 3 meals and 2 snacks different for each day of the 3-week cycle, with repeating cycles. All KD-treated participants will receive the same meal plan. Meals will be prepared uniformly by one facility and will be delivered to participants frozen once a week in packages subdivided into individual days with each day's package containing 5 separately packaged meals. Participants will be given a list of allowed 0 calories drinks and will consume no non-allowed beverages. Reductions to oral glycemic medications will occur at the start of the diet.

Participants will be evaluated in face-to-face visit during weeks 1, 2 and 4 of the study, then monthly (see Table 1, visit schedule). Evaluations will include weight, BMI, BP, waist circumference, adverse events and treatment compliance. Participants will check their blood glucose levels 3x/day, including am fasting, mid-day and evening 2 hours post-prandial, and urine for ketones levels with Ketostix (Bayer AG, IN, U.S.A.) 2x/day. They will record results in a glucose and ketone level diary which will be reviewed at each visit. Laboratory evaluations will include 8 am serum fasting glucose, insulin levels, C-peptide and lipid panel, HbA1C, serum beta-hydroxybutyrate (BOH), leptin levels, C-reactive protein (CRP), complete blood count (CBC), basic metabolic profile (BMP), renal and liver functions tests (LFTs), and uric acid. Laboratory evaluations will be obtained once at baseline prior to treatment initiation, at 3 and 6 months after treatment initiation. Hunger will be evaluated with a 7-point Likert scale (range: extremely hungry to extremely full) which will be administered at each visit.

Eligibility criteria: Inclusion Criteria:

1. Age 18-70
2. Ability and willingness to sign informed consent form.
3. T2D with BMI ≥ 30 kg/m2
4. Stable hypoglycemic medications for at least 2 months

Exclusion Criteria:

1. History of bariatric surgery ≤ 2 years prior to enrollment.
2. Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, unstable metabolic or endocrine disturbances, renal or liver disease, past history of renal calculi, hyperuricemia, hypercalcemia, mitochondrial disease, known disorder of fatty acid metabolism, porphyria, and active systemic cancer.
3. History of uncontrolled hyperlipidemia
4. Change in the dose or type of hypoglycemic treatment within 1 month prior to enrollment.
5. Psychosis within six months of enrollment, evidenced by treatment with anti-psychotic medications with recent medication initiation or dose increase.
6. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements;
7. History of cerebrovascular disease or unstable heart disease within 6 months of enrollment
8. Pregnancy
9. Use of any investigational drugs within 3 months of enrollment.
10. Inability or unwillingness of subject to give written informed consent.

Primary outcomes:
measure: Type 2 diabetes remission
timeFrame: 6 months (study duration)
Secondary outcomes:
measure: Change from baseline in glucose blood level in patients with type 2 DM in 6 months.
timeFrame: 6 months (study duration)
measure: Percentage of diabetic medication load reduction
timeFrame: 6 months (study duration)
measure: Change from baseline in HbA1C in patients with type 2 DM in 6 months.
timeFrame: 0, 3 and 6 months treatment duration
measure: Adverse events
timeFrame: 6 months (study duration)
measure: Fasting serum insulin
timeFrame: 0, 3 and 6 months treatment duration
measure: BMI
timeFrame: Day 0, Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
measure: Weight
timeFrame: Day 0, Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
measure: Waist circumference
timeFrame: Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
measure: Blood pressure
timeFrame: Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
measure: Urine ketone levels
timeFrame: Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
measure: Fasting leptin levels
timeFrame: 0, 3 and 6 months treatment duration
measure: Fasting lipid levels
timeFrame: 0, 3 and 6 months treatment duration
measure: Hunger scale scores
timeFrame: Day 0, Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Ivana Tyrlikova
state: Maryland
Study officials:
affiliation: Mid-Atlantic Epilepsy and Sleep Center
name: Pavel Klein, M.B,B.Chir.
role: PRINCIPAL_INVESTIGATOR
References: