Metabolism of Low Carbohydrate and Ketogenic Diet

• ClinicalTrials.gov Identifier: NCT05071287
• Recruitment Status: Active, not recruiting
• First Posted: October 8, 2021
• Last Update Posted: July 5, 2022
• Sponsor: The University of Texas Health Science Center at San Antonio
• Information provided by (Responsible Party): The University of Texas Health Science Center at San Antonio

Tracking Information

• First Submitted Date: August 24, 2021
• First Posted Date: October 8, 2021
• Last Update Posted Date: July 5, 2022
• Actual Study Start Date: June 3, 2021
• Actual Primary Completion Date: April 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 27, 2021)

• Estimated Glomerular Filtration rate (eGFR) [ Time Frame: Baseline to 6 months ]
  Measure of change in eGFR in a blood sample
• Albumin-to-Creatinine ratio (ACR) [ Time Frame: Baseline to 6 months ]
  Measure of the change in ACR in urine
• Mitochondrial DNA [ Time Frame: Baseline to 6 months ]
  Measure of change of mitochondrial function using blood and urine levels
• Montreal Cognitive Assessment (MoCA) [ Time Frame: Baseline to 6 months ]
  A one page, 30-point test administered to test cognition. MoCA scores range between 0 and 30. A score of 26 or over is considered to have no cognitive impairment, while lower scores imply more cognitive impairment. Tasks include short term memory recall, visuospatial ability tests, attention, concentration and working memory evaluation and language skills.
• Gut Metabolomics [ Time Frame: Baseline to 6 months ]
  Measure of changes of gut metabolites using mass spectroscopy

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 27, 2021)

Glycemic Control [ Time Frame: Baseline to 6 months ]

Change in glycemic control measured by the change in percentage of glycated hemoglobin in blood

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: November 2, 2021)

• Weight Change [ Time Frame: Baseline to 6 months ]
  Measure of weight change that occurred while assigned to the diet
• Change in Blood Pressure [ Time Frame: Baseline to 6 months ]
  Measure of blood pressure change that occurs over study period, both systolic and diastolic.
• Total blood lipids [ Time Frame: Baseline to 6 months ]
  Measure of change in total blood lipids over the study period
• Fecal Metabolomics [ Time Frame: Baseline to 6 months ]
  Measure of changes of fecal metabolites in optional stool sample using mass spectroscopy

Original Other Pre-specified Outcome Measures (submitted: September 27, 2021)

• Weight Change [ Time Frame: Baseline to 6 months ]
  Measure of weight change that occurred while assigned to the diet
• Change in Blood Pressure [ Time Frame: Baseline to 6 months ]
  Measure of blood pressure change that occurs over study period
• Total blood lipids [ Time Frame: Baseline to 6 months ]
  Measure of change in total blood lipids over the study period
• Fecal Metabolomics [ Time Frame: Baseline to 6 months ]
  Measure of changes of fecal metabolites in optional stool sample using mass spectroscopy

Descriptive Information

• Brief Title: Metabolism of Low Carbohydrate and Ketogenic Diet
• Official Title: Precision Metabolic Mechanisms of Low Carbohydrate and Ketogenic Diet
• Brief Summary: This study will assess the preliminary efficacy of a lifestyle intervention including low-carb/ketogenic diet and exercise, enhanced by self-monitoring through health technologies on weight and diabetes outcomes (Glucose, HbA1c) and diabetic complications (cognitive function, and renal function) in a 6-month randomized clinical trial in 60 overweight/obese adults with or without T2D. Renal function will be assessed via both traditional and novel biomarkers, including novel metabolites and mitochondrial function.

Detailed Description

Participants in both groups will receive standardized health education sessions including lifestyle management, blood glucose control, blood pressure control, and prevention of diabetic complications from trained providers who are also investigators of this study. The lifestyle intervention from the evidence-based Group Lifestyle Balance (GLB) program (http://www.diabetesprevention.pitt.edu/index.php/for-the-public/for-health-providers/group-lifestyle-balance-curriculum/) and Look AHEAD intervention (https://www.lookaheadtrial.org) will be modified for this study. Goal for weight loss and physical activity will be set for each participant based on recommendations from GLB and Look AHEAD. Lifestyle intervention will be delivered through interactive digital lessons. Smart phone and mobile health devices will be used for each participant to self-monitor diet, physical activity, weight, glucose level, blood pressure, and blood ketone (if randomized to the low-car/ketogenic diet group).

Control group (mHealth+ low-fat diet group):

The low-fat group will be asked to restrict total calorie and total fat consumption according to the Look AHEAD intervention and MyPlate guidelines, with 26-44% carbs, 10-30% protein, and less than 30% fat.

Intervention group (mHealth+ low-carb/ketogenic diet group):

The low-carb/ketogenic diet group, will have total calorie set according to Look AHEAD intervention, and carb consumption restriction will be set based on recommendations from American Diabetic Association, National Kidney Foundation, and other evidence-based resources. Participants in this group will be asked to consume a low-carb/ketogenic diet. Specially, participants will receive a carbohydrate, protein, and fat intake goal based on 1.5 : 1 ratio (1.5 grams of fat to 1 gram of carbohydrate and protein combined). Daily macronutrient and calorie consumption will be individualized for each participant using ideal body weight as inferred from wrist circumference and activity level. Carbohydrate consumption will be less than 10% (20~50 g), protein 10-20% (1.0~1.2g/kg ideal body weight), and fat 70-80% of total daily energy, respectively. Nutritional ketosis will be reached by consuming such diet (0.5 mmol/L).

All diet intervention materials will be developed by a registered dietitian according to the evidence-based guidelines. The dietitian will also be responsible to any study activities relevant to diet. These activities include but are not limited to responding to some specific diet questions to study participants and health related measurements relevant to diet changes.

An interventionist, under supervision of a registered dietitian, will interact with each participant from both groups at the beginning of the intervention as an introduction visit, and three individual intervention sessions at month 1, 3, and 5. During the introduction visit, the interventionist will set up a personalized weight loss goal and caloric intake goal with the participants. The individual intervention sessions at month 1, 3 and 5 will be arranged to solve the encountered problems regarding diet, weight loss, caloric intake and action planning.

Additional communication through phone call will be used to support patient dietary changes throughout the study based on their self-monitoring information.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized controlled trial with 2 arms. Randomization will be done in clusters:

1. overweight/obese adults with type 2 diabetes (T2D) but no chronic kidney disease (CKD)
2. overweight/obese with T2D without CKD
3. overweight/obese with early stage CKD

Masking: None (Open Label)
Primary Purpose: Other

Condition

• Diabetic Kidney Disease
• Cognitive Function
• Weight Loss
• Diabetic Control
• Type2 Diabetes

Intervention

• Other: mHealth + low-fat diet
  A restricted total calorie and reduced total fat consumption.
• Other: mHealth + low-carb/ketogenic diet
  A low-carb/ketogenic diet

Study Arms

• Placebo Comparator: Control Group (mHealth+low-fat diet group)
  The low-fat group will be asked to restrict total calorie and total fat consumption according to the Look AHEAD intervention and MyPlate guidelines, with 26-44% carbs, 10-30% protein, and less than 30% fat.
  Intervention: Other: mHealth + low-fat diet
• Experimental: Intervention Group (mHealth + low-carbohydrate/ketogenic diet group)
  Total calories will be set according to Look AHEAD intervention, and carbohydrate consumption restriction will be set based on recommendations from American Diabetic Association, National Kidney Foundation, and other evidence-based resources. Participants in this group will be asked to consume a low-carb/ketogenic diet. Specially, participants will receive a carbohydrate, protein, and fat intake goal based on 1.5 : 1 ratio (1.5 grams of fat to 1 gram of carbohydrate and protein combined). Daily macronutrient and calorie consumption will be individualized for each participant using ideal body weight as inferred from wrist circumference and activity level. Carbohydrate consumption will be less than 10% (20~50 g), protein 10-20% (1.0~1.2g/kg ideal body weight), and fat 70-80% of total daily energy, respectively. Nutritional ketosis will be reached by consuming such diet (0.5 mmol/L).
  Intervention: Other: mHealth + low-carb/ketogenic diet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: September 27, 2021): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2023
• Actual Primary Completion Date: April 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Willing to participate in the study
2. being 18 and over

3. For overweight/obese adults (BMI≥25kg/m2)

   1. without self-reported diagnosis of Type 2 Diabetes (T2D) or Chronic Kidney Disease (CKD): Estimated Glomerular Filtration Rate (eGFR)≥90mL/min/1.73m2 and urine albumin to creatinine ratio (ACR)<30mg/g within the past 12 months
   2. with Type 2 Diabetes (T2D) but without Chronic Kidney Disease (CKD): Estimated glomerular filtration rate (eGFR)≥90mL/min/1.73m2 and Albumin-to-Creatinine ratio (ACR)<30mg/g within the past 12 months
   3. with early stage Chronic Kidney Disease (CKD): 60≤eGFR<90mL/min/1.73m2 or 30mg/g ≤ACR< 1000mg/g within the 12 months
4. can speak and understand English
5. own a smart phone or tablet that has reliable internet/data access
6. agree to comply with all study requirements

Exclusion Criteria:

1. Patients with triglyceride ≥ 500 mg/dL or with Low-Density Lipoprotein Cholesterol≥ 129mg/dL
2. type 1 diabetes (by self-report)
3. severe psychiatric disorders deemed by investigators, which might interfere with study procedures (by self-report)
4. severe chronic conditions (e.g. severe heart disease, renal disease, cognitive impairment, etc.) that would preclude them from participating
5. unwillingness to sign the consent form and be randomized into a study group
6. enrollment in other low carb/keto diet or weight loss programs
7. inability to walk without assistance (by self-report)
8. under SGLT2 inhibitor treatment
9. being pregnant or breast feeding (by self-report)
10. having plans to leave the city or USA for over 2 weeks within 6 months at enrollment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05071287
• Other Study ID Numbers: HSC20190528H
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: The plan to make Individual Participant Data (IPD) available to other researchers has not been decided.

• Current Responsible Party: The University of Texas Health Science Center at San Antonio
• Original Responsible Party: Same as current
• Current Study Sponsor: The University of Texas Health Science Center at San Antonio
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Yan Du, PhD MPH RN; University of Texas Health San Antonio

• PRS Account: The University of Texas Health Science Center at San Antonio
• Verification Date: July 2022