Investigating the Production of Lipoproteins and Acetyl-CoA During a Ketogenic Diet (PLAK)

• ClinicalTrials.gov Identifier: NCT03901014
• Recruitment Status: Active, not recruiting
• First Posted: April 3, 2019
• Last Update Posted: October 6, 2021
• Sponsor: Touro University, California
• Information provided by (Responsible Party): Touro University, California

Study Description

Brief Summary:

The purpose of this study is to understand how the reduction in dietary carbohydrates in a very-low carbohydrate ketogenic diet impacts the synthesis of cholesterol, fatty acid, and ketones, and the turnover rate of VLDL and chylomicron particles.

Condition or disease	Intervention/treatment	Phase
Cholesterol Metabolism; Ketone Metabolism	Other: Standard American diet; Other: Very low carbohydrate diet	Not Applicable

Detailed Description:

Participants will consume a standard American diet for one week followed by a very-low carbohydrate ketogenic diet (VLCKD, <50 grams carbohydrate/day) for two weeks. Participants will undergo an oral stable isotope tracer study during each diet to measure de novo synthesis of fatty acid, cholesterol, ketone bodies, and for measurement of apolipoprotein B and triglyceride kinetics.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Masking Description: The nature of the diet does not allow for masking
• Primary Purpose: Basic Science
• Official Title: Investigating the Production of Lipoproteins and Acetyl-CoA During a Ketogenic Diet
• Actual Study Start Date: March 31, 2019
• Actual Primary Completion Date: April 18, 2019
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Baseline diet; 1 week baseline diet	Other: Standard American diet; Standard American diet with 50% energy from carbohydrate, 30% from fat, and 20% from protein.
Experimental: Very low carbohydrate diet; 2 week very low carbohydrate ketogenic diet	Other: Very low carbohydrate diet; Ketogenic diet with <50g carbohydrate, 60-75% energy from fat, and 20% from protein

Outcome Measures

Primary Outcome Measures :

1. Change in total cholesterol [ Time Frame: Day 3-7 to Day 17-21 ]
   Change in serum total cholesterol between Day 3-7 (average value) to Day 17-21 (average value)
2. Change in low density lipoprotein (LDL) cholesterol [ Time Frame: Day 3-7 to Day 17-21 ]
   Change in serum LDL cholesterol between Day 3-7 (average value) to Day 17-21 (average value)
3. Change in high density lipoprotein (HDL) cholesterol [ Time Frame: Day 3-7 to Day 17-21 ]
   Change in serum HDL cholesterol between Day 3-7 (average value) to Day 17-21 (average value)
4. Change in apolipoprotein B (apoB) kinetics [ Time Frame: Day 3-7 to Day 17-21 ]
   Change in apoB turnover rates in LDL and very low density lipoprotein plasma fractions as measured using 2H2 leucine incorporation into apoB and mathematical modeling

Secondary Outcome Measures :

1. Change in fractional hepatic de novo lipogenesis [ Time Frame: Day 3 to Day 17 ]
   Measured by the detection of incorporated 1-13C sodium acetate into palmitate in triglyceride rich lipoproteins (TRL)
2. Change in fractional cholesterol synthesis [ Time Frame: Day 3 to Day 17 ]
   Measured by the detection of incorporated 1-13C sodium acetate into cholesterol in plasma
3. Change in ketone body synthesis [ Time Frame: Day 3 to Day 17 ]
   Measured by the detection of incorporated 1-13C sodium acetate into ketone bodies in plasma
4. Change in TRL-triglyceride kinetics [ Time Frame: Day 3 to Day 17 ]
   Change in TRL- triglyceride assembly rates as measured using 2-13C glycerol and mathematical modeling
5. Change in triglyceride lipolysis [ Time Frame: Day 3 to Day 17 ]
   Measured by the dilution of administered 2-13C glycerol in plasma
6. Change in serum glucose concentration [ Time Frame: Day 3 to Day 17 ]
   Change in fasting and postprandial serum glucose levels
7. Change in serum free fatty acid concentration [ Time Frame: Day 3 to Day 17 ]
   Change in fasting and postprandial serum free fatty acid levels
8. Change in serum insulin concentration [ Time Frame: Day 3 to Day 17 ]
   Change in fasting and postprandial serum insulin levels
9. Change in serum ketone body concentration [ Time Frame: Day 3 to Day 17 ]
   Change in fasting and postprandial ketone body levels

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male
• 18-50 years old

Exclusion Criteria:

• Use of nicotine products
• Has dietary restrictions
• Lactose intolerance
• History of GI disorders, diabetes, liver, kidney, or thyroid disorders
• Taking hypolipidemic, anti-diabetic, anti-hypertensive, or anti-depression medication
• Screening plasma triglyceride < 50mg/dl or >500mg/dl
• Screening glucose > 125mg/dl
• Screening total and LDL-Cholesterol over 95th %tile for age and sex
• BP > 160/95 mmHg
• Weight loss/gain > 5% in the previous 3 months (self-reported)

Contacts and Locations

Locations

United States, California

Touro University California

Vallejo, California, United States, 94592

Sponsors and Collaborators

Touro University, California

Investigators

• Principal Investigator: Grace M Jones, PhD; Touro University, California

More Information

• Responsible Party: Touro University, California
• ClinicalTrials.gov Identifier: NCT03901014
• Other Study ID Numbers: M-0419
• First Posted: April 3, 2019
• Last Update Posted: October 6, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Touro University, California:

ketogenic diet; LDL cholesterol; carbohydrate