Monounsaturated Fatty Acid Supplementation for Overweight and Obese Individuals With Prediabetes

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05560971
• Other study ID #: 2022P001764
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: January 2024
• Source: Brigham and Women's Hospital
• Contact: Lindsey Porter
• Phone: 781-879-0796
• Email: lmporter[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Glucose Intolerance
• Insulin Resistance
• Obesity
• Overweight
• PreDiabetes
• Prediabetic State

Intervention

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:
• Placebo
Medium chain fatty acids in triglyceride form in capsules with the same shape, color, size and odor of POA capsules

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Tersus Life Sciences LLC

Country where clinical trial is conducted

United States, 

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* Note: There are 36 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity M value change before and 8 weeks after POA vs placebo intake	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	Modified mixed meal tolerance test	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
Secondary	Liver fat quantification	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
Secondary	Total body fat mass and body composition	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
Secondary	Serum; fasting glucose, insulin, LDL cholesterol, hsCRP, circulating inflammatory cytokines (TNF-a, IL-6), FABP4, glucagon	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