Pro-resolving Effect of MAG-DHA in Cystic Fibrosis (PREMDIC)

Cystic Fibrosis Clinical Trial

— PREMDIC  

Official title:

Role of DHA Monoglyceride (MAG-DHA) in the Resolution of Pulmonary Inflammation of Patients With Cystic Fibrosis.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02518672
• Other study ID #: 14-108
• Status: Terminated
• Phase: Phase 2
• First received: August 3, 2015
• Last updated: October 3, 2017
• Start date: October 2015
• Est. completion date: November 2016

Study information

• Verified date: October 2017
• Source: SCF Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Monoglyceride of DHA (DHA-MAG) is a lipid compound for which intestinal absorption would increase the ratio DHA / arachidonic acid (AA) and promote the synthesis of specific metabolites involved in the resolution of inflammation.

The PREMDIC project, initiated at the Centre Hospitalier Universitaire de Sherbrooke, is a randomized double-blind study for people with cystic fibrosis (CF) and aims to evaluate whether daily supplementation monoglyceride of DHA (a fatty acid omega-3 family) will reduce lung inflammation and improve pulmonary function.

Description:

The goal of the study is:

To investigate the efficacity of oral administration of MAG-DHA to increase DHA bioavailability and reduce lung inflammation of patients with cystic fibrosis

The specific objectives of the project are :

• Determine the effect of MAG-DHA on lipid membranes of the blood mononuclear cells.

• Evaluate the effect of MAG-DHA on lung inflammation (determination of Human leukocyte elastase and alpha1 antitrypsin complexes : pHLE).

For this study, 20 cystic fibrosis patients are recruited. Patients are divided into 2 groups of 10 and received a daily dose equivalent to 3 g of placebo (sunflower oil) or MAG-DHA.

The project takes place over a period of 3 months and patients must travel to the research center for a total of five visits including recruitment.

For the 2 groups, DHA ratio / AA is measured in membranes of mononuclear cells. Forced expiratory volume in 1 second (FEV1) is determined and pHLE complexes are detected in plasma as a marker of inflammation.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: November 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. forced expiratory volume in 1 second (FEV1) between 30 - 90%.

2. no respiratory exacerbations during the last 2 weeks before the start of the study

3. not have clotting problems or a history of bleeding diathesis

4. patients with liver function abnormalities are included in the study

Exclusion Criteria:

1. pregnant women or those not using contraception.

2. known allergy to fish and / or seafood.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Dietary Supplement:
• MAG-DHA
MAG-DHA 8 x 625 mg softgels by mouth, every day at bedtime for 90 days.
• Placebo
Placebo (sunflower oil) 8 x 625 mg softgels by mouth, every day at bedtime for 90 days.

Locations

Country	Name	City	State
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec

Sponsors (3)

Lead Sponsor	Collaborator
SCF Pharma	Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Solutex (Spain)

Country where clinical trial is conducted

Canada, 

References & Publications (15)

Al-Turkmani MR, Freedman SD, Laposata M. Fatty acid alterations and n-3 fatty acid supplementation in cystic fibrosis. Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):309-18. Epub 2007 Nov 26. Review. — View Citation

Andersson C, Al-Turkmani MR, Savaille JE, Alturkmani R, Katrangi W, Cluette-Brown JE, Zaman MM, Laposata M, Freedman SD. Cell culture models demonstrate that CFTR dysfunction leads to defective fatty acid composition and metabolism. J Lipid Res. 2008 Aug;49(8):1692-700. doi: 10.1194/jlr.M700388-JLR200. Epub 2008 Apr 25. — View Citation

Cantin A. Cystic fibrosis lung inflammation: early, sustained, and severe. Am J Respir Crit Care Med. 1995 Apr;151(4):939-41. — View Citation

Cantin AM, Bilodeau G, Larivée P, Richter MV. Plasma biomarkers and cystic fibrosis lung disease. Clin Invest Med. 2012 Jul 4;35(4):E173-81. — View Citation

Dyerberg J, Madsen P, Møller JM, Aardestrup I, Schmidt EB. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids. 2010 Sep;83(3):137-41. doi: 10.1016/j.plefa.2010.06.007. — View Citation

Fortin S, Compositions comprising polyunsaturated fatty acid monoglycerides or derivatives thereof and uses thereof, US819690, 2012, US8222295, 2012.

Fortin S, Polyunsaturated fatty acid monoglycerides, derivatives, and uses thereof, CA2672513, 2008, CA2677670, 2010, US8119690, 2011.

Freedman SD, Katz MH, Parker EM, Laposata M, Urman MY, Alvarez JG. A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr(-/-) mice. Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13995-4000. — View Citation

Mimoun M, Coste TC, Lebacq J, Lebecque P, Wallemacq P, Leal T, Armand M. Increased tissue arachidonic acid and reduced linoleic acid in a mouse model of cystic fibrosis are reversed by supplemental glycerophospholipids enriched in docosahexaenoic acid. J Nutr. 2009 Dec;139(12):2358-64. doi: 10.3945/jn.109.110999. Epub 2009 Oct 14. — View Citation

Morin C, Cantin AM, Rousseau É, Sirois M, Sirois C, Rizcallah E, Fortin S. Proresolving Action of Docosahexaenoic Acid Monoglyceride in Lung Inflammatory Models Related to Cystic Fibrosis. Am J Respir Cell Mol Biol. 2015 Oct;53(4):574-83. doi: 10.1165/rcm — View Citation

Morin C, Fortin S, Cantin AM, Rousseau E. Docosahexaenoic acid derivative prevents inflammation and hyperreactivity in lung: implication of PKC-Potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kD in asthma. Am J Respir Cell Mol Biol. 2011 Aug;45(2):366-75. doi: 10.1165/rcmb.2010-0156OC. Epub 2010 Nov 5. — View Citation

Morin C, Fortin S, Cantin AM, Sirois M, Sirois C, Rizcallah E, Rousseau É. Anti-cancer effects of a new docosahexaenoic acid monoacylglyceride in lung adenocarcinoma. Recent Pat Anticancer Drug Discov. 2013 Sep;8(3):319-34. — View Citation

Panchaud A, Sauty A, Kernen Y, Decosterd LA, Buclin T, Boulat O, Hug C, Pilet M, Roulet M. Biological effects of a dietary omega-3 polyunsaturated fatty acids supplementation in cystic fibrosis patients: a randomized, crossover placebo-controlled trial. Clin Nutr. 2006 Jun;25(3):418-27. Epub 2005 Dec 2. — View Citation

Pier G, Prince A, Cantin A. Cystic fibrosis: an-ion transport issue? Nat Med. 2011 Feb;17(2):166-7. doi: 10.1038/nm0211-166. — View Citation

Vij N, Mazur S, Zeitlin PL. CFTR is a negative regulator of NFkappaB mediated innate immune response. PLoS One. 2009;4(2):e4664. doi: 10.1371/journal.pone.0004664. Epub 2009 Feb 27. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lung and systemic inflammation measurement	Docosahexaenoic acid (DHA) and metabolites lipid analyses in plasma and red blood cells Human leukocyte elastase and alpha1 antitrypsin complexes detection in plasma Pulmonary function test (spirometry): Forced Expiratory Volume in 1 second (FEV1) and Forced Vital Capacity (FVC) Leukocytes differential cell counts and C reactive protein (CRP) determination level in blood	0 and 90 days
Secondary	follow up of vital signs	weight (Kg)	0 and 90 days
Secondary	follow up of vital signs	Body Mass Index (BMI, Kg/cm2)	0 and 90 days
Secondary	follow up of vital signs	Blood Pressure (mmHg)	0 and 90 days
Secondary	lipid profile	triglycerides (mmol/l)	0 and 90 days
Secondary	lipid profile	cholesterol (mmol/l)	0 and 90 days
Secondary	lipid profile	high density lipoprotein (mmol/l)	0 and 90 days
Secondary	lipid profile	low density lipoprotein (mmol/l)	0 and 90 days
Secondary	hepatic function	measurement of Alanine aminotransferase (ALT) in plasma (U/l)	0 and 90 days
Secondary	hepatic function	measurement of Aspartate aminotransferase (AST) in plasma (U/l)	0 and 90 days
Secondary	hepatic function	measurement of Gamma glutamyl transpeptidase in plasma (U/l)	0 and 90 days