Monounsaturated Fatty Acid Supplementation for Overweight and Obese Individuals With Prediabetes

January 17, 2024 updated by: Mehmet F. Burak, MD, Brigham and Women's Hospital

The Effect of Palmitoleic Acid (POA) Supplementation on Insulin Sensitivity and Lipogenesis in Overweight and Obese Individuals

The purpose of this study is to understand and determine whether Palmitoleic acid (POA), monounsaturated omega-7 fatty acid (exists in regular diet), improves insulin sensitivity and decreases liver fat accumulation in humans. Unlike others, the study will use POA as a dietary supplement, rather than complex oils, which contain a significant amount of saturated fat palmitic acid. Palmitic acid has known harmful effects on the body. Hence, eliminating palmitic acid from supplementation of POA might increase its benefits. This trial stems from the preclinical discoveries that POA acting as a fat hormone, has beneficial effects on the liver, muscle, vessels, and fat tissue. Supporting this, higher POA levels in humans have been shown to be correlated with a reduced risk of developing type-2 diabetes and cardiovascular diseases such as heart attacks. In animals, it has been observed that POA improves sugar metabolism in a number of mechanisms related to the liver and muscle. Based on these findings, the design of this study is a double-blind placebo-controlled trial that tests the effects of POA on insulin sensitivity of overweight and obese adult individuals with pre-diabetes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Specific aims of the study are as follows: 1) To test whether supplementation of POA, as compared to placebo, improves insulin sensitivity. 2) To test whether supplementation of POA, as compared to placebo, ameliorates hepatosteatosis and decreases whole-body fat mass, serum triglyceride, and LDL cholesterol. 3)To determine whether supplementation of POA, as compared to placebo, decreases plasma levels of fasting glucose, insulin, FABP4, glucagon, inflammatory cytokines, and hsCRP.

The investigators will recruit overweight and obese individuals (BMI 25-40) with mild insulin resistance, prediabetes and/or impaired glucose tolerance. The study is powered only for the primary endpoint, insulin sensitivity. After the screening visit confirms the eligibility for the study; the investigators will perform an oral glucose tolerance test (OGTT) for stratified randomization for better homogeneity between POA and placebo groups. The investigators aim to have 40 participants complete the study which will consist of 2 main overnight visits consisting of an insulin clamp procedure and a mixed meal tolerance test the night prior. Participants will also have a liver MRI and DEXA scan at these two visits. Participants will be asked to consume a palmitoleic acid minimized diet for 10 weeks which will start two weeks before the first overnight visit. This research study will compare insulin sensitivity before and 8 weeks after taking POA vs placebo in the same individuals. After the first overnight visit participants will be given either POA or placebo capsules to take daily for 8 weeks until the second overnight visit. There will also be a short blood draw visit 4 weeks after the first overnight visit.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Overweight and obese individuals with prediabetes and/or impaired glucose tolerance
  • Age 18 to 70 years
  • BMI 25-40 kg/m2
  • HbA1c between 5.6 - 6.5, Impaired fasting plasma glucose levels (>99, ≤126 mg/dL) or OGTT blood glucose at 2 hours between 140-200 mg/dL or HOMA-IR >2.5
  • BP <150/90 with or without medication
  • GFR>60
  • ALT, AST <300
  • Normal thyroid function is defined as screening TSH within normal ranges, with or without medication

Exclusion Criteria:

  • Use of any medications (except thyroid hormone with normal TSH, anti-hypertensives with blood pressure <150/90 and non-steroidal rescue inhalers for asthma)
  • Pregnancy or breastfeeding
  • Use of over-the-counter (OTC) supplements (except vitamin D). The investigators will ensure that study participants are not using supplements containing fish oil or other lipid supplements (e.g., macadamia oil, krill oil, flaxseed, primrose oil, sea buckthorn oil) within 3 months of study participation
  • Greater than 3 servings/day combined of cheese, whole-fat milk, kefir, or whole-fat yogurt for the last 3 months before the study.
  • Diagnosed with any type of diabetes mellitus and/or taking glucose-lowering medications
  • Recent weight loss (more than 7% of total body weight loss in last 3 months)
  • Established major chronic diseases such as major cardiovascular disease (history of myocardial infarction, stroke, symptomatic heart failure, coronary artery bypass graft, Atrial fibrillation, symptomatic peripheral arterial disease), bleeding disorder or anticoagulation use, active cancer, end-stage renal disease, proteinuria (>3g/day), dementia, severe chronic obstructive pulmonary disease (needs systemic steroid therapy), significant liver disease (ALT or AST>300)
  • History of ongoing smoking cigarettes >1 pack/day, alcohol abuse, or illicit drug abuse
  • Treatment with any investigational drug in the one month preceding the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Palmitoleic acid
The treatment arm will receive Palmitoleic acid (POA) supplement as Provinal® 420 mg capsules with at least 90% pure POA Ethyl Ester (less than 1% palmitic acid). Participants will be asked to consume 2 Provinal® 420 mg capsules twice a day for 8 weeks.
Dietary supplement: Palmitoleic acid
Participants will be randomized to either POA or placebo and will be asked to take 2 capsules of the POA or placebo twice a day for 8 weeks.
Other Names:
  • Provinal®
Placebo Comparator: Placebo
The placebo is a medium chain fatty acid in triglyceride form. The placebo has no shown health effects, neither beneficial or detrimental. Participants will be asked to consume 2 placebo capsules daily twice a day for 8 weeks.
Other: Placebo
Medium chain fatty acids in triglyceride form in capsules with the same shape, color, size and odor of POA capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin sensitivity M value change before and 8 weeks after POA vs placebo intake
Time Frame: 8 weeks
Insulin sensitivity (M values) will be evaluated by hyperinsulinemic euglycemic clamp (gold standard) from the same individuals before and after taking POA vs. placebo. The investigators will compare M values before and after taking POA vs placebo intake. Hence the investigators are looking for delta changes and expect 20% statistically significant improvement with POA and no significant change with placebo. The investigators calculated sample size and powered the study for only this primary endpoint to see at least 20% difference.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modified mixed meal tolerance test
Time Frame: 8 weeks
The investigators will measure glucose and c-peptide response to standard mixed meal. Study participants will ingest the mixed meal and then the investigators will measure glucose and c-peptide levels from venous blood collected every 30 minutes for 2 hours. Area under the curve (AUC) for both glucose and c-peptide will be calculated and this value from same individuals before and 8 weeks after POA vs placebo intake will be compared.
8 weeks
Liver fat quantification
Time Frame: 8 weeks
Liver fat percent will be evaluated by liver MRI-PDFF (proton density fat fraction). Blinded radiologist will analyze the MRI fat fraction and use standard ROI gating. The investigators will compare % fat fraction (FF) from same individuals before and 8 weeks after POA vs placebo intake
8 weeks
Total body fat mass and body composition
Time Frame: 8 weeks
Body composition, which is whole-body fat vs lean mass will be evaluated by DEXA scan. Whole-body % fat mass from same individuals before and 8 weeks after POA vs placebo intake will be compared.
8 weeks
Serum; fasting glucose, insulin, LDL cholesterol, hsCRP, circulating inflammatory cytokines (TNF-a, IL-6), FABP4, glucagon
Time Frame: 8 weeks
The investigoators will compare serum fasting glucose, insulin, LDL cholesterol, hsCRP, circulating inflammatory cytokines (TNF-a, IL-6), FABP4, glucagon from same individuals before and 8 weeks after POA vs placebo intake
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Tersus Life Sciences LLC

Investigators

  • Principal Investigator: Mehmet Furkan Burak, MD, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2022

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

September 27, 2022

First Submitted That Met QC Criteria

September 29, 2022

First Posted (Actual)

September 30, 2022

Study Record Updates

Last Update Posted (Estimated)

January 19, 2024

Last Update Submitted That Met QC Criteria

January 17, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022P001764

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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