Effect of EPA and DHA in the Inflammation and Metabolic Disorders in DMD/DMB Patients

Muscular Dystrophy, Duchenne Clinical Trial

Official title:

Effect of Eicosapentaenoic Fatty Acid (EPA) and Docosahexaenoic Fatty Acids (DHA) Supplementation on the Inflammation State and Metabolic Disorders in Patients With Duchenne Muscular Dystrophy or Becker Muscular Dystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01826422
• Other study ID #: DHA/EPA in Dunchenne
• Secondary ID: 180058
• Status: Completed
• Phase: N/A
• First received: April 4, 2013
• Last updated: February 8, 2018
• Start date: March 2013
• Est. completion date: January 2017

Study information

• Verified date: February 2018
• Source: Coordinación de Investigación en Salud, Mexico
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effect of docosahexaenoic fatty acid and eicosapentaenoic fatty acid supplementation for six months on the inflammation state as well as the process of muscular regeneration and the metabolic disorders like obesity and insulin resistance in patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (DMB) compared to those receiving placebo.

Description:

DMD and DMB are X-linked diseases caused by mutations in the DMD gene, these mutations have important functional and structural consequences in skeletal muscle. In muscle fiber is observed inflammation and necrosis as a result of lost regenerative capacity. The muscle fibers can be replaced by connective and adipose tissue. In a previous study the investigators identified that 50% of Duchenne and Becker patients in the range of thirteen years old have obesity. In addition, these patients (N=66) have hyperinsulinemia (53.7%) and insulin resistance (48.5%). It is well known that obesity, hyperinsulinemia and insulin resistance have a inflammatory background.

It has been demonstrated that eicosapentaenoic fatty acid (EPA) and docosahexaenoic fatty acid (DHA) exhibit anti-inflammatory properties and have beneficial effects on obesity, hyperinsulinemia and insulin resistance in children and adolescents.

Objective: Determine the effect of EPA and DHA on inflammation, obesity and insulin resistance in patients with DMD/DMB compared to those receiving placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years to 18 Years

Eligibility

Inclusion Criteria:

• Written informed consent and assent by the patient and both parents or guardian.

• Patients with clinical diagnosis of Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (DMB)

• Patients were not under treatment with corticosteroids

Exclusion Criteria:

• Patients decided to withdraw from the study

• Consumption of dietary supplements containing polyunsaturated fatty acids omega 3.

• With hypersensitivity to fish oil.

• Patients with respiratory and gastrointestinal problems. Medical responsible assessment the presence of respiratory and gastrointestinal problems.

• Patients with difficulty swallowing food, including those who have the difficulty ingesting oil capsules.

• Gastrostomy fed patients.

Related Conditions & MeSH terms

• Inflammation
• Metabolic Diseases
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Dietary Supplement:
• EPA and DHA
Each capsule contains 225mg of DHA, 45mg of EPA, other omega 3 fatty acids 20mg.
• Placebo Comparator
Placebo capsules will contain gelatin and sunflower oil. Fatty acid composition is as follows: lauric (C12:0), 0.19%; myristic (C14:0), 0.29%; palmitic (C16:0), 7.59%; palmitoleic (C16:1), 0.25%; stearic (C18:0), 3.49%; oleic (C18:1), 31.08%; linolenic (C18:3), 1.13%; linoleic (C18:2), 55.64%; DHA 0.02%; arachidic (C20:0), 0.30% and arachidonic (C20:4), 0.01%.

Locations

Country	Name	City	State
Mexico	Unit of Medical Researcha in Nutrition, Pediatric Hospital, IMSS.	Mexico city

Sponsors (2)

Lead Sponsor	Collaborator
Coordinación de Investigación en Salud, Mexico	Instituto Nacional de Rehabilitacion

Country where clinical trial is conducted

Mexico, 

References & Publications (3)

Cruz Guzmán Odel R, Chávez García AL, Rodríguez-Cruz M. Muscular dystrophies at different ages: metabolic and endocrine alterations. Int J Endocrinol. 2012;2012:485376. doi: 10.1155/2012/485376. Epub 2012 Jun 3. — View Citation

Rodríguez-Cruz M, Cruz-Guzmán ODR, Almeida-Becerril T, Solís-Serna AD, Atilano-Miguel S, Sánchez-González JR, Barbosa-Cortés L, Ruíz-Cruz ED, Huicochea JC, Cárdenas-Conejo A, Escobar-Cedillo RE, Yam-Ontiveros CA, Ricárdez-Marcial EF. Potential therapeutic — View Citation

Rodríguez-Cruz M, Sanchez R, Escobar RE, Cruz-Guzmán Odel R, López-Alarcón M, Bernabe García M, Coral-Vázquez R, Matute G, Velázquez Wong AC. Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy. Int J Endocrinol. 2015;2015:867273. doi: 10.1155/2015/867273. Epub 2015 May 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body Composition (Body Fat)	We observed changes in body composition such as total body fat by Dual X-ray Absorptiometry (DXA).	At baseline and at months 3 and 6 of supplementation.
Primary	Lean Mass	We observed changes in body composition such as total lean mass by Dual X-ray Absorptiometry (DXA).	At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.
Primary	Anthropometric Measurement: Body Mass Index	We measured weight, height by anthropometric to calculate the body mass index (body mass index).	At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.
Primary	Glucose in Serum	A fasting blood sample was taken; serum glucose (mg/dL) levels were measured by the glucose-oxidase method.	At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.
Primary	Insulin in Blood	A fasting blood sample was taken; insulin was quantified utilizing a commercial kit, that is based on the radioimmunoanalysis method (RIA).	At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.
Secondary	Inflammation Biomarkers (TNF-A)	Plasma cytokine TNF-A was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Inflammation Biomarkers (IL-1)	Plasma cytokine IL-1 was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Inflammation Biomarkers (IL-6)	Plasma cytokine IL-6 was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.	Time Frame: At baseline and at months 1, 2, 3, and 6 of supplementation.
Secondary	Inflammation Biomarkers (IL-10)	Plasma cytokine IL-10 was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Inflammation Biomarker (IL-6 Expression)	The messenger ribonucleic acid (mRNA) expression of cytokines IL-6 from circulating leucocytes was determined by quantifying the real-time polymerase chain reaction (PCR).	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Inflammation Biomarker (TNF-A Expression)	The messenger ribonucleic acid (mRNA) expression of cytokines TNF-A from circulating leucocytes was determined by quantifying the real-time polymerase chain reaction (PCR)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Inflammation Biomarker (IL-1 Expression)	The messenger ribonucleic acid (mRNA) expression of cytokines IL-1 was determined by quantifying the real-time polymerase chain reaction (PCR).	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Markers of Muscle Degeneration (Creatinine Kinase)	The concentration in serum of CK was determined by chemiluminescent immunometric assay in U/L.	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Markers of Muscle Degeneration (MMP9)	Plasma matrix metalloproteinase 9 (MMP9) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in ng/mL.	Time Frame: At baseline and at months 1, 2, 3 of supplementation.
Secondary	Markers of Muscle Degeneration (sFas)	The concentration in plasma of soluble Fas (sFas) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Markers of Muscle Degeneration (Receptor of Fas)	The concentration in plasma of the receptor o Fas (rFas) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.	At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Markers of Muscle Regeneration (VEGF)	Vascular endothelial growth factor (VEGF) was quantified using enzyme linked immunosorbent assay (ELISA).	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Markers of Muscle Regeneration (FGF)	Plasma marker of regeneration fibroblast growth factor basic (FGF) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.
Secondary	Incorporation of DHA in the Erythrocytes	The percentage of DHA in the membrane of erythrocytes was determinated by gas chromatography.	Time Frame: At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.
Secondary	Incorporation of EPA in the Erythrocytes	The percentage of EPA in the membrane of erythrocytes was determinated by gas chromatography.	Time Frame: At baseline, at 1, 2, 3, 4, 5, and 6