Treatment of Type 2 Diabetes With Ketogenic Diet

Evaluation of Efficacy and Safety of Ketogenic Complete Meal Replacement as Treatment of Obesity-related Type 2 Diabetes Mellitus

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.

Study Overview

• Status: Unknown
• Conditions: Obesity; Type2 Diabetes Mellitus
• Intervention / Treatment: Other: 3:1 ratio Ketogenic 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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ivana Tyrlikova; Phone Number: 3015309744; Email: tyrlikovai@epilepsydc.com
• Study Contact Backup: Name: Lenka Goldman; Phone Number: 3015309744

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • Ivana Tyrlikova
      • Principal Investigator: Pavel Klein, MD
      • Contact: Ivana Tyrlikova, MD; Phone Number: 301-530-9744; Email: tyrlikovai@epilepsydc.com
      • Contact: Pavel Klein, MD; Phone Number: 3015309744; Email: kleinp@epilepsydc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3:1 Ketogenic Complete Meal Replacement; 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 complete meal replacement ketogenic diet	Other: 3:1 ratio Ketogenic diet; Type 2 Diabetic subjects with BMI greater than or equal to 30 are started on 3:1 ratio ketogenic complete meal replacement program and weight loss and glycemic control is tracked over 6 month intervention period; Other Names: Classic Ketogenic Diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type 2 diabetes remission	Defined as normal fasting blood glucose (<126), normal HbA1C (<6.4%), and no diabetic medications	6 months (study duration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in glucose blood level in patients with type 2 DM in 6 months.	Defined as normal fasting blood glucose (<126), normal HbA1C (<6.4%), and no diabetic medications	6 months (study duration)
Percentage of diabetic medication load reduction	Change in diabetic medication load	6 months (study duration)
Change from baseline in HbA1C in patients with type 2 DM in 6 months.	HbA1C	0, 3 and 6 months treatment duration
Adverse events	Adverse events occurrence	6 months (study duration)
Fasting serum insulin	Change in fasting serum insulin value	0, 3 and 6 months treatment duration
BMI	Change BMI from baseline	Day 0, Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
Weight	Change weight from baseline	Day 0, Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
Waist circumference	Change waist circumference from baseline	Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
Blood pressure	Change of systolic and diastolic blood pressures from baseline	Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
Urine ketone levels	Urine ketone levels evaluation	Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6
Fasting leptin levels	Fasting leptin levels evaluation	0, 3 and 6 months treatment duration
Fasting lipid levels	Fasting lipid levels evaluation	0, 3 and 6 months treatment duration
Hunger scale scores	Likert scale (range: extremely hungry to extremely full) which will be administered at each visit.The best outcome is 5=satisfied.	Day 0, Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6

Collaborators and Investigators

• Sponsor: Mid-Atlantic Epilepsy and Sleep Center, LLC
• Investigators: Principal Investigator: Pavel Klein, M.B,B.Chir., Mid-Atlantic Epilepsy and Sleep Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: July 5, 2018
• First Submitted That Met QC Criteria: August 28, 2018
• First Posted (Actual): August 29, 2018

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 28, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: diabetes; obesity; nutrition; type 2 diabetes; weight loss; ketogenic diet; BMI; low carb diet; diet treatment
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Obesity
• Other Study ID Numbers: maes 009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No