Title
Effect of EPA and DHA in the Inflammation and Metabolic Disorders in DMD/DMB Patients
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
Phase
Phase 2Lead Sponsor
Government of MexicoStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Muscular Dystrophy, DuchenneIntervention/Treatment
icosapent ethyl fish oil ...Study Participants
40The 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.
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.
Each capsule contains 225mg of DHA, 45mg of EPA, other omega 3 fatty acids 20mg.
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%.
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.
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.
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.
| Event Type | Organ System | Event Term | EPA and DHA | Sunflower Oil |
|---|
A fasting blood sample was taken; serum glucose (mg/dL) levels were measured by the glucose-oxidase method.
A fasting blood sample was taken; insulin was quantified utilizing a commercial kit, that is based on the radioimmunoanalysis method (RIA).
We observed changes in body composition such as total body fat by Dual X-ray Absorptiometry (DXA).
We observed changes in body composition such as total lean mass by Dual X-ray Absorptiometry (DXA).
We measured weight, height by anthropometric to calculate the body mass index (body mass index).
The percentage of DHA in the membrane of erythrocytes was determinated by gas chromatography.
The percentage of EPA in the membrane of erythrocytes was determinated by gas chromatography.
Plasma cytokine TNF-A was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
Plasma cytokine IL-1 was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
Plasma cytokine IL-6 was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
Plasma cytokine IL-10 was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
The messenger ribonucleic acid (mRNA) expression of cytokines IL-6 from circulating leucocytes was determined by quantifying the real-time polymerase chain reaction (PCR).
The messenger ribonucleic acid (mRNA) expression of cytokines TNF-A from circulating leucocytes was determined by quantifying the real-time polymerase chain reaction (PCR)
The messenger ribonucleic acid (mRNA) expression of cytokines IL-1 was determined by quantifying the real-time polymerase chain reaction (PCR).
Plasma matrix metalloproteinase 9 (MMP9) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in ng/mL.
The concentration in serum of CK was determined by chemiluminescent immunometric assay in U/L.
The concentration in plasma of soluble Fas (sFas) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
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.
Vascular endothelial growth factor (VEGF) was quantified using enzyme linked immunosorbent assay (ELISA).
Plasma marker of regeneration fibroblast growth factor basic (FGF) was determined by enzyme-linked immunosorbent assay (ELISA) with a multiplex kit in picograms/mL.
