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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05560971
Other study ID # 2022P001764
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
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
Health authority
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

Study Design


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, 

References & Publications (36)

Adler GK, Hornik ES, Murray G, Bhandari S, Yadav Y, Heydarpour M, Basu R, Garg R, Tirosh A. Acute effects of the food preservative propionic acid on glucose metabolism in humans. BMJ Open Diabetes Res Care. 2021 Jul;9(1):e002336. doi: 10.1136/bmjdrc-2021-002336. — View Citation

Bang HO, Dyerberg J, Hjoorne N. The composition of food consumed by Greenland Eskimos. Acta Med Scand. 1976;200(1-2):69-73. doi: 10.1111/j.0954-6820.1976.tb08198.x. — View Citation

Bolsoni-Lopes A, Festuccia WT, Chimin P, Farias TS, Torres-Leal FL, Cruz MM, Andrade PB, Hirabara SM, Lima FB, Alonso-Vale MI. Palmitoleic acid (n-7) increases white adipocytes GLUT4 content and glucose uptake in association with AMPK activation. Lipids Health Dis. 2014 Dec 20;13:199. doi: 10.1186/1476-511X-13-199. — View Citation

Burak MF, Inouye KE, White A, Lee A, Tuncman G, Calay ES, Sekiya M, Tirosh A, Eguchi K, Birrane G, Lightwood D, Howells L, Odede G, Hailu H, West S, Garlish R, Neale H, Doyle C, Moore A, Hotamisligil GS. Development of a therapeutic monoclonal antibody that targets secreted fatty acid-binding protein aP2 to treat type 2 diabetes. Sci Transl Med. 2015 Dec 23;7(319):319ra205. doi: 10.1126/scitranslmed.aac6336. Epub 2015 Dec 23. — View Citation

Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell. 2008 Sep 19;134(6):933-44. doi: 10.1016/j.cell.2008.07.048. — View Citation

Cao H, Sekiya M, Ertunc ME, Burak MF, Mayers JR, White A, Inouye K, Rickey LM, Ercal BC, Furuhashi M, Tuncman G, Hotamisligil GS. Adipocyte lipid chaperone AP2 is a secreted adipokine regulating hepatic glucose production. Cell Metab. 2013 May 7;17(5):768-78. doi: 10.1016/j.cmet.2013.04.012. — View Citation

Chan KL, Pillon NJ, Sivaloganathan DM, Costford SR, Liu Z, Theret M, Chazaud B, Klip A. Palmitoleate Reverses High Fat-induced Proinflammatory Macrophage Polarization via AMP-activated Protein Kinase (AMPK). J Biol Chem. 2015 Jul 3;290(27):16979-88. doi: 10.1074/jbc.M115.646992. Epub 2015 May 18. — View Citation

Cimen I, Kocaturk B, Koyuncu S, Tufanli O, Onat UI, Yildirim AD, Apaydin O, Demirsoy S, Aykut ZG, Nguyen UT, Watkins SM, Hotamisligil GS, Erbay E. Prevention of atherosclerosis by bioactive palmitoleate through suppression of organelle stress and inflammasome activation. Sci Transl Med. 2016 Sep 28;8(358):358ra126. doi: 10.1126/scitranslmed.aaf9087. — View Citation

Curb JD, Wergowske G, Dobbs JC, Abbott RD, Huang B. Serum lipid effects of a high-monounsaturated fat diet based on macadamia nuts. Arch Intern Med. 2000 Apr 24;160(8):1154-8. doi: 10.1001/archinte.160.8.1154. — View Citation

de Souza CO, Teixeira AAS, Biondo LA, Lima Junior EA, Batatinha HAP, Rosa Neto JC. Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPARalpha-Dependent AMPK Activation. J Cell Physiol. 2017 Aug;232(8):2168-2177. doi: 10.1002/jcp.25715. Epub 2017 Mar 24. — View Citation

de Souza CO, Valenzuela CA, Baker EJ, Miles EA, Rosa Neto JC, Calder PC. Palmitoleic Acid has Stronger Anti-Inflammatory Potential in Human Endothelial Cells Compared to Oleic and Palmitic Acids. Mol Nutr Food Res. 2018 Oct;62(20):e1800322. doi: 10.1002/mnfr.201800322. Epub 2018 Aug 28. — View Citation

Dimopoulos N, Watson M, Sakamoto K, Hundal HS. Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells. Biochem J. 2006 Nov 1;399(3):473-81. doi: 10.1042/BJ20060244. — View Citation

Duckett SK, Volpi-Lagreca G, Alende M, Long NM. Palmitoleic acid reduces intramuscular lipid and restores insulin sensitivity in obese sheep. Diabetes Metab Syndr Obes. 2014 Nov 20;7:553-63. doi: 10.2147/DMSO.S72695. eCollection 2014. — View Citation

Dyerberg J, Bang HO, Hjorne N. Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr. 1975 Sep;28(9):958-66. doi: 10.1093/ajcn/28.9.958. — View Citation

Garg ML, Blake RJ, Wills RB. Macadamia nut consumption lowers plasma total and LDL cholesterol levels in hypercholesterolemic men. J Nutr. 2003 Apr;133(4):1060-3. doi: 10.1093/jn/133.4.1060. — View Citation

Gravena C, Mathias PC, Ashcroft SJ. Acute effects of fatty acids on insulin secretion from rat and human islets of Langerhans. J Endocrinol. 2002 Apr;173(1):73-80. doi: 10.1677/joe.0.1730073. — View Citation

Griel AE, Cao Y, Bagshaw DD, Cifelli AM, Holub B, Kris-Etherton PM. A macadamia nut-rich diet reduces total and LDL-cholesterol in mildly hypercholesterolemic men and women. J Nutr. 2008 Apr;138(4):761-7. doi: 10.1093/jn/138.4.761. — View Citation

Guo X, Jiang X, Chen K, Liang Q, Zhang S, Zheng J, Ma X, Jiang H, Wu H, Tong Q. The Role of Palmitoleic Acid in Regulating Hepatic Gluconeogenesis through SIRT3 in Obese Mice. Nutrients. 2022 Apr 1;14(7):1482. doi: 10.3390/nu14071482. — View Citation

Hiraoka-Yamamoto J, Ikeda K, Negishi H, Mori M, Hirose A, Sawada S, Onobayashi Y, Kitamori K, Kitano S, Tashiro M, Miki T, Yamori Y. Serum lipid effects of a monounsaturated (palmitoleic) fatty acid-rich diet based on macadamia nuts in healthy, young Japanese women. Clin Exp Pharmacol Physiol. 2004 Dec;31 Suppl 2:S37-8. doi: 10.1111/j.1440-1681.2004.04121.x. — View Citation

Imamura F, Fretts A, Marklund M, Ardisson Korat AV, Yang WS, Lankinen M, Qureshi W, Helmer C, Chen TA, Wong K, Bassett JK, Murphy R, Tintle N, Yu CI, Brouwer IA, Chien KL, Frazier-Wood AC, Del Gobbo LC, Djousse L, Geleijnse JM, Giles GG, de Goede J, Gudnason V, Harris WS, Hodge A, Hu F; InterAct Consortium; Koulman A, Laakso M, Lind L, Lin HJ, McKnight B, Rajaobelina K, Riserus U, Robinson JG, Samieri C, Siscovick DS, Soedamah-Muthu SS, Sotoodehnia N, Sun Q, Tsai MY, Uusitupa M, Wagenknecht LE, Wareham NJ, Wu JH, Micha R, Forouhi NG, Lemaitre RN, Mozaffarian D; Fatty Acids and Outcomes Research Consortium (FORCE). Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. PLoS Med. 2018 Oct 10;15(10):e1002670. doi: 10.1371/journal.pmed.1002670. eCollection 2018 Oct. — View Citation

Kampmann U, Mosekilde L, Juhl C, Moller N, Christensen B, Rejnmark L, Wamberg L, Orskov L. Effects of 12 weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function, and metabolic markers in patients with type 2 diabetes and vitamin D insufficiency - a double-blind, randomized, placebo-controlled trial. Metabolism. 2014 Sep;63(9):1115-24. doi: 10.1016/j.metabol.2014.06.008. Epub 2014 Jun 19. — View Citation

Lima EA, Silveira LS, Masi LN, Crisma AR, Davanso MR, Souza GI, Santamarina AB, Moreira RG, Martins AR, de Sousa LG, Hirabara SM, Rosa Neto JC. Macadamia oil supplementation attenuates inflammation and adipocyte hypertrophy in obese mice. Mediators Inflamm. 2014;2014:870634. doi: 10.1155/2014/870634. Epub 2014 Sep 22. — View Citation

Maedler K, Oberholzer J, Bucher P, Spinas GA, Donath MY. Monounsaturated fatty acids prevent the deleterious effects of palmitate and high glucose on human pancreatic beta-cell turnover and function. Diabetes. 2003 Mar;52(3):726-33. doi: 10.2337/diabetes.52.3.726. — View Citation

Maedler K, Spinas GA, Dyntar D, Moritz W, Kaiser N, Donath MY. Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function. Diabetes. 2001 Jan;50(1):69-76. doi: 10.2337/diabetes.50.1.69. — View Citation

Mozaffarian D, Cao H, King IB, Lemaitre RN, Song X, Siscovick DS, Hotamisligil GS. Circulating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes. Am J Clin Nutr. 2010 Dec;92(6):1350-8. doi: 10.3945/ajcn.110.003970. Epub 2010 Oct 13. — View Citation

Olefsky JM. Fat talks, liver and muscle listen. Cell. 2008 Sep 19;134(6):914-6. doi: 10.1016/j.cell.2008.09.001. — View Citation

Pinnick KE, Neville MJ, Fielding BA, Frayn KN, Karpe F, Hodson L. Gluteofemoral adipose tissue plays a major role in production of the lipokine palmitoleate in humans. Diabetes. 2012 Jun;61(6):1399-403. doi: 10.2337/db11-1810. Epub 2012 Apr 9. — View Citation

Riserus U, Willett WC, Hu FB. Dietary fats and prevention of type 2 diabetes. Prog Lipid Res. 2009 Jan;48(1):44-51. doi: 10.1016/j.plipres.2008.10.002. Epub 2008 Nov 7. — View Citation

Stefan N, Kantartzis K, Celebi N, Staiger H, Machann J, Schick F, Cegan A, Elcnerova M, Schleicher E, Fritsche A, Haring HU. Circulating palmitoleate strongly and independently predicts insulin sensitivity in humans. Diabetes Care. 2010 Feb;33(2):405-7. doi: 10.2337/dc09-0544. Epub 2009 Nov 4. — View Citation

Tang J, Yang B, Yan Y, Tong W, Zhou R, Zhang J, Mi J, Li D. Palmitoleic Acid Protects against Hypertension by Inhibiting NF-kappaB-Mediated Inflammation. Mol Nutr Food Res. 2021 Jun;65(12):e2001025. doi: 10.1002/mnfr.202001025. Epub 2021 May 10. — View Citation

Tovar R, Gavito AL, Vargas A, Soverchia L, Hernandez-Folgado L, Jagerovic N, Baixeras E, Ciccocioppo R, Rodriguez de Fonseca F, Decara J. Palmitoleoylethanolamide Is an Efficient Anti-Obesity Endogenous Compound: Comparison with Oleylethanolamide in Diet-Induced Obesity. Nutrients. 2021 Jul 28;13(8):2589. doi: 10.3390/nu13082589. — View Citation

Trico D, Mengozzi A, Nesti L, Hatunic M, Gabriel Sanchez R, Konrad T, Lalic K, Lalic NM, Mari A, Natali A; EGIR-RISC Study Group. Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis. Diabetologia. 2020 Jan;63(1):206-218. doi: 10.1007/s00125-019-05013-6. Epub 2019 Nov 1. — View Citation

Tripathy D, Wessman Y, Gullstrom M, Tuomi T, Groop L. Importance of obtaining independent measures of insulin secretion and insulin sensitivity during the same test: results with the Botnia clamp. Diabetes Care. 2003 May;26(5):1395-401. doi: 10.2337/diacare.26.5.1395. — View Citation

Weimann E, Silva MBB, Murata GM, Bortolon JR, Dermargos A, Curi R, Hatanaka E. Topical anti-inflammatory activity of palmitoleic acid improves wound healing. PLoS One. 2018 Oct 11;13(10):e0205338. doi: 10.1371/journal.pone.0205338. eCollection 2018. — View Citation

Yang ZH, Miyahara H, Hatanaka A. Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK-Ay Mice with genetic type 2 diabetes. Lipids Health Dis. 2011 Jul 21;10:120. doi: 10.1186/1476-511X-10-120. Erratum In: Lipids Health Dis. 2021 Aug 24;20(1):90. — View Citation

Yang ZH, Takeo J, Katayama M. Oral administration of omega-7 palmitoleic acid induces satiety and the release of appetite-related hormones in male rats. Appetite. 2013 Jun;65:1-7. doi: 10.1016/j.appet.2013.01.009. Epub 2013 Jan 30. — View Citation

* Note: There are 36 references in allClick 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
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