Contrasting Ketogenic and Mediterranean Diets in Individuals With Type 2 Diabetes and Prediabetes: The Keto-Med Trial

Sponsor

Stanford University (Other)

Overall Status

Completed

CT.gov ID

NCT03810378

Collaborator

(none)

Enrollment

Location

Arms

18.1

Actual Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this study is to compare two metabolically distinct diets, WFKD vs Med-Plus, in order to examine the potential benefits, and unintended consequences, of going beyond a focus on maximally avoiding added sugars and refined grains, to also avoiding legumes, fruits, and whole grains.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2 PreDiabetes	Behavioral: Mediterranean Diet (Med-Plus) Behavioral: Well-Formulated Ketogenic Diet (WFKD)	N/A

Detailed Description

The proposed randomized clinical trial will investigate differential population-specific effects of two low-carbohydrate (low-carb) diet patterns, addressing a gap in the evidence base in this area that will lead to 1) improved treatment strategies for common adverse clinical conditions, 2) improved health for these individuals, and 3) long-term decreases in health care costs. This impactful research will advance the field of personalized and precision medicine.

Study Design

Study Type:

Interventional

Actual Enrollment :

61 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

40 adults will be randomized in cross-over design to a Ketogenic or Mediterranean diet for 12 weeks each (no washout) with a 1 month follow-up at the end of the second phase.40 adults will be randomized in cross-over design to a Ketogenic or Mediterranean diet for 12 weeks each (no washout) with a 1 month follow-up at the end of the second phase.

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Contrasting Ketogenic and Mediterranean Diets in Individuals With Type 2 Diabetes and Prediabetes: The Keto-Med Trial

Actual Study Start Date :

Jun 5, 2019

Actual Primary Completion Date :

Dec 4, 2020

Actual Study Completion Date :

Dec 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mediterranean Diet (Med-Plus) Participants will follow a Mediterranean-type diet (Med-Plus) for 12 weeks. This diet will maximize the intake of vegetables, legumes, fruits and nuts, whole intact grains/cereals and fish; and minimize the intake of meat, poultry, and dairy. It will exclude added sugars and refined grains.	Behavioral: Mediterranean Diet (Med-Plus) Participants will follow the Med-Plus diet for 12 weeks, then switch to the alternate diet for another 12 weeks (no washout period).
Experimental: Well-Formulated Ketogenic Diet (WFKD) Participants will follow a Well-Formulated Ketogenic Diet (WFKD) for 12 weeks. This diet will maximize the intake of non-processed beef, pork, and poultry (preferably organic/grass-fed), fish, heavy cream, low-lactose, high-fat cheeses, animal fats, oils (avocado, coconut, or other nut oils), non-starchy (above ground) vegetables and limited amounts of some fruits (berries). It will exclude legumes, grains, sugars, starchy (below ground) vegetables, most fruits, and polyunsaturated oils (soy, sunflower, peanut, cottonseed, canola, etc.). It will aim for an intake of 20 g of carbohydrates/day at start, with the goal to have no more than 50 grams/day to maintain ketosis.	Behavioral: Well-Formulated Ketogenic Diet (WFKD) Participants will follow the WFKD diet for 12 weeks, then switch to the alternate diet for another 12 weeks (no washout period).

Arm

Intervention/Treatment

Experimental: Mediterranean Diet (Med-Plus)

Participants will follow a Mediterranean-type diet (Med-Plus) for 12 weeks. This diet will maximize the intake of vegetables, legumes, fruits and nuts, whole intact grains/cereals and fish; and minimize the intake of meat, poultry, and dairy. It will exclude added sugars and refined grains.

Behavioral: Mediterranean Diet (Med-Plus)

Participants will follow the Med-Plus diet for 12 weeks, then switch to the alternate diet for another 12 weeks (no washout period).

Experimental: Well-Formulated Ketogenic Diet (WFKD)

Participants will follow a Well-Formulated Ketogenic Diet (WFKD) for 12 weeks. This diet will maximize the intake of non-processed beef, pork, and poultry (preferably organic/grass-fed), fish, heavy cream, low-lactose, high-fat cheeses, animal fats, oils (avocado, coconut, or other nut oils), non-starchy (above ground) vegetables and limited amounts of some fruits (berries). It will exclude legumes, grains, sugars, starchy (below ground) vegetables, most fruits, and polyunsaturated oils (soy, sunflower, peanut, cottonseed, canola, etc.). It will aim for an intake of 20 g of carbohydrates/day at start, with the goal to have no more than 50 grams/day to maintain ketosis.

Behavioral: Well-Formulated Ketogenic Diet (WFKD)

Participants will follow the WFKD diet for 12 weeks, then switch to the alternate diet for another 12 weeks (no washout period).

Outcome Measures

Primary Outcome Measures

Hemoglobin A1c (HbA1c) [Baseline and 12 weeks]
Change from baseline in HbA1c at 12 weeks of each phase

Secondary Outcome Measures

Microbiota composition [Baseline and 12 weeks]
Change from baseline in alpha diversity at 12 weeks of each phase. We will be using number of observed sequence variants ("species") determined by standard 16S rRNA amplicon sequencing (V3-V5 region followed by DADA2 to define error-corrected sequence variants) as our primary metric of alpha diversity. Higher alpha diversity is better. The units are the # of sequence variants.
Microbiota function [Baseline and 12 weeks]
Change from baseline in composite of short-chain fatty acids (SCFA) concentration (ug/g stool: acetate + propionate + butyrate) at 12 weeks of each phase.
LDL Cholesterol [Baseline and12 weeks]
Change from baseline in LDL cholesterol at 12 weeks of each phase.
HDL Cholesterol [Baseline and 12 weeks]
Change from baseline in HDL cholesterol at 12 weeks of each phase.
Triglycerides [Baseline and 12 weeks]
Change from baseline in triglycerides at 12 weeks of each phase.
Fasting insulin [Baseline and 12 weeks]
Change from baseline in fasting insulin at 12 weeks of each phase.
Blood pressure [Baseline and 12 weeks]
Change from baseline in blood pressure at 12 weeks of each phase.

Other Outcome Measures

Satisfaction with WFKD and Med-Plus diets [Baseline and 12 weeks]
Average satisfaction level with meals at 12 weeks of each phase (WFKD compared to Med-Plus phase) using a 5-point Likert scale (1=not at all satisfied; 2=slightly satisfied; 3=moderately satisfied; 4=very satisfied; 5=extremely satisfied).
Adherence to diet protocols [Baseline and 12 weeks]
Adherence to diet protocols 12 weeks of each phase in subjects with Diabetes compared to subjects with prediabetes, according to 3-day food records.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age ≥18
Diagnosed with type 2 diabetes mellitus, OR prediabetes (defined as HbA1c </= 5.7% OR Fasting Glucose of >100 mg/dL)

Identify exclusion criteria.

Weight < 110 lb
BMI > 40
LDL-C >190 mg/dL
Blood pressure: SBP > 160 mmHg OR DBP: > 90 mmHg

Exclusion Criteria:

Weight < 110 lb
BMI ≥ 40
LDL-C >190 mg/dL
Systolic blood pressure (SBP) > 160 mmHg OR Diastolic blood pressure (DBP) > 90 mmHg
Diagnosed with type 1 diabetes or history of ketoacidosis
Uncontrolled and untreated diabetes (by discretion of study physician)
Active cardiovascular disease (in past year with myocardial infarction, coronary stent or bypass surgery)
Kidney disease (eGFR less than 50 mL/min per 1.73 m2)
Liver disease (liver transaminase higher than 3 times the normal range for the laboratory)
Symptomatic gallstones
History of bariatric surgery
Anemia
Taking any of the following medications in past 3 months: SGLT-2 inhibitors, GLP-1 receptor agonist, Insulin, Amylin analog, Alpha-glucosidase inhibitor, Dopamine agonist, Bile acid sequestrant.
Taking any medications for weight loss
History of active cancer in the past 3 years except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision
Unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet.
Recent history of chronic excessive alcohol consumption defined as more than five 1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer or five 5-ounce servings of wine per day; or > 14 drinks/week.
Women: Pregnant currently or planning to become pregnant during the course of the study, and/or breastfeeding
Regular/frequent use of smoking or chewing tobacco, e-cigarettes, cigars or other nicotine-containing products
Regular use of prescription opiate pain medication