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

Not Applicable

Completed

Conditions: Muscular Dystrophy, Duchenne

Interventions: Dietary Supplement: EPA and DHA
Dietary Supplement: Placebo Comparator

Registration Number: NCT01826422

Lead Sponsor: Coordinación de Investigación en Salud, Mexico

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 40

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EPA and DHA	EPA and DHA	Supplementation of 2.7 g/d of EPA and DHA were provided in 10 capsules per day (4 in the morning, 3 in the afternoon and 3 at night) during a period of 6 months. The capsules sizes were specially for children to improved the feeding process and its presentation is in gelatin capsules. The supplement is purified fish oil with pharmaceutical grade.
Placebo Comparator	Placebo Comparator	Supplementation of placebo with sunflower fatty at doses of 2.7 g/d were provided in 10 capsules per day (4 in the morning, 3 in the afternoon and 3 at night) during a period of 6 months. The capsules sizes are specially for children to improved the feeding process. This placebo is sunflower oil, so, it did not present anti-inflammatory or insulin sensitivity effects.

Primary Outcome Measures

Name	Time	Method
Body Composition (Body Fat)	At baseline and at months 3 and 6 of supplementation.	We observed changes in body composition such as total body fat by Dual X-ray Absorptiometry (DXA).
Lean Mass	At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.	We observed changes in body composition such as total lean mass by Dual X-ray Absorptiometry (DXA).
Anthropometric Measurement: Body Mass Index	At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.	We measured weight, height by anthropometric to calculate the body mass index (body mass index).
Glucose in Serum	At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.	A fasting blood sample was taken; serum glucose (mg/dL) levels were measured by the glucose-oxidase method.
Insulin in Blood	At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.	A fasting blood sample was taken; insulin was quantified utilizing a commercial kit, that is based on the radioimmunoanalysis method (RIA).

Secondary Outcome Measures

Name	Time	Method
Inflammation Biomarkers (TNF-A)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	Plasma cytokine TNF-A was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
Inflammation Biomarkers (IL-1)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	Plasma cytokine IL-1 was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
Inflammation Biomarkers (IL-6)	Time Frame: At baseline and at months 1, 2, 3, and 6 of supplementation.	Plasma cytokine IL-6 was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
Inflammation Biomarkers (IL-10)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	Plasma cytokine IL-10 was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
Inflammation Biomarker (IL-6 Expression)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	The messenger ribonucleic acid (mRNA) expression of cytokines IL-6 from circulating leucocytes was determined by quantifying the real-time polymerase chain reaction (PCR).
Inflammation Biomarker (TNF-A Expression)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	The messenger ribonucleic acid (mRNA) expression of cytokines TNF-A from circulating leucocytes was determined by quantifying the real-time polymerase chain reaction (PCR)
Inflammation Biomarker (IL-1 Expression)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	The messenger ribonucleic acid (mRNA) expression of cytokines IL-1 was determined by quantifying the real-time polymerase chain reaction (PCR).
Markers of Muscle Degeneration (Creatinine Kinase)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	The concentration in serum of CK was determined by chemiluminescent immunometric assay in U/L.
Markers of Muscle Degeneration (MMP9)	Time Frame: At baseline and at months 1, 2, 3 of supplementation.	Plasma matrix metalloproteinase 9 (MMP9) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in ng/mL.
Markers of Muscle Degeneration (sFas)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	The concentration in plasma of soluble Fas (sFas) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
Markers of Muscle Degeneration (Receptor of Fas)	At baseline and at months 1, 2, 3 and 6 of supplementation.	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.
Markers of Muscle Regeneration (VEGF)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	Vascular endothelial growth factor (VEGF) was quantified using enzyme linked immunosorbent assay (ELISA).
Markers of Muscle Regeneration (FGF)	Time Frame: At baseline and at months 1, 2, 3 and 6 of supplementation.	Plasma marker of regeneration fibroblast growth factor basic (FGF) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
Incorporation of DHA in the Erythrocytes	Time Frame: At baseline and at months 1, 2, 3, 4, 5 and 6 of supplementation.	The percentage of DHA in the membrane of erythrocytes was determinated by gas chromatography.
Incorporation of EPA in the Erythrocytes	Time Frame: At baseline, at 1, 2, 3, 4, 5, and 6	The percentage of EPA in the membrane of erythrocytes was determinated by gas chromatography.