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

Primary Purpose

Diabetes Mellitus, Type 2, PreDiabetes

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Mediterranean Diet (Med-Plus)

Well-Formulated Ketogenic Diet (WFKD)

About this trial

This is an interventional prevention trial for Diabetes Mellitus, Type 2 focused on measuring Ketogenic diet, Mediterranean diet, Diabetes, Prediabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Stanford University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Mediterranean Diet (Med-Plus)

Well-Formulated Ketogenic Diet (WFKD)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Hemoglobin A1c (HbA1c)

Change from baseline in HbA1c at 12 weeks of each phase

Secondary Outcome Measures

Microbiota composition

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

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

Change from baseline in LDL cholesterol at 12 weeks of each phase.

HDL Cholesterol

Change from baseline in HDL cholesterol at 12 weeks of each phase.

Triglycerides

Change from baseline in triglycerides at 12 weeks of each phase.

Fasting insulin

Change from baseline in fasting insulin at 12 weeks of each phase.

Blood pressure

Change from baseline in blood pressure at 12 weeks of each phase.

Full Information

NCT ID

NCT03810378

First Posted

January 9, 2019

Last Updated

February 18, 2023

Sponsor

Stanford University

1. Study Identification

Unique Protocol Identification Number

NCT03810378

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

June 5, 2019 (Actual)

Primary Completion Date

December 4, 2020 (Actual)

Study Completion Date

December 6, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Stanford University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2, PreDiabetes

Keywords

Ketogenic diet, Mediterranean diet, Diabetes, Prediabetes

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

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.

Masking

InvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

61 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mediterranean Diet (Med-Plus)

Arm Type

Experimental

Arm Description

Arm Title

Well-Formulated Ketogenic Diet (WFKD)

Arm Type

Experimental

Arm Description

Intervention Type

Behavioral

Intervention Name(s)

Mediterranean Diet (Med-Plus)

Intervention Description

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

Intervention Type

Behavioral

Intervention Name(s)

Well-Formulated Ketogenic Diet (WFKD)

Intervention Description

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

Primary Outcome Measure Information:

Title

Hemoglobin A1c (HbA1c)

Description

Change from baseline in HbA1c at 12 weeks of each phase

Time Frame

Baseline and 12 weeks

Secondary Outcome Measure Information:

Title

Microbiota composition

Description

Time Frame

Baseline and 12 weeks

Title

Microbiota function

Description

Change from baseline in composite of short-chain fatty acids (SCFA) concentration (ug/g stool: acetate + propionate + butyrate) at 12 weeks of each phase.

Time Frame

Baseline and 12 weeks

Title

LDL Cholesterol

Description

Change from baseline in LDL cholesterol at 12 weeks of each phase.

Time Frame

Baseline and12 weeks

Title

HDL Cholesterol

Description

Change from baseline in HDL cholesterol at 12 weeks of each phase.

Time Frame

Baseline and 12 weeks

Title

Triglycerides

Description

Change from baseline in triglycerides at 12 weeks of each phase.

Time Frame

Baseline and 12 weeks

Title

Fasting insulin

Description

Change from baseline in fasting insulin at 12 weeks of each phase.

Time Frame

Baseline and 12 weeks

Title

Blood pressure

Description

Change from baseline in blood pressure at 12 weeks of each phase.

Time Frame

Baseline and 12 weeks

Other Pre-specified Outcome Measures:

Title

Satisfaction with WFKD and Med-Plus diets

Description

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).

Time Frame

Baseline and 12 weeks

Title

Adherence to diet protocols

Description

Adherence to diet protocols 12 weeks of each phase in subjects with Diabetes compared to subjects with prediabetes, according to 3-day food records.

Time Frame

Baseline and 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christopher Gardner, PhD

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35641199

Citation

Gardner CD, Landry MJ, Perelman D, Petlura C, Durand LR, Aronica L, Crimarco A, Cunanan KM, Chang A, Dant CC, Robinson JL, Kim SH. Effect of a ketogenic diet versus Mediterranean diet on glycated hemoglobin in individuals with prediabetes and type 2 diabetes mellitus: The interventional Keto-Med randomized crossover trial. Am J Clin Nutr. 2022 Sep 2;116(3):640-652. doi: 10.1093/ajcn/nqac154. Erratum In: Am J Clin Nutr. 2022 Dec 19;116(6):1904.

Results Reference

background

PubMed Identifier

33802709

Citation

Landry MJ, Crimarco A, Perelman D, Durand LR, Petlura C, Aronica L, Robinson JL, Kim SH, Gardner CD. Adherence to Ketogenic and Mediterranean Study Diets in a Crossover Trial: The Keto-Med Randomized Trial. Nutrients. 2021 Mar 17;13(3):967. doi: 10.3390/nu13030967.

Results Reference

derived

Links:

URL

https://med.stanford.edu/nutrition/research/completed-studies/KETOMEDstudy.html

Description

Study description and summary of results

Learn more about this trial

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

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