Effect of DHA on Lipid and Carbohydrate Metabolism Alterations and Body Fat Distribution in HIV Patients Under HAART.

• Status: Completed
• Trial end date: 2013-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Highly active antiretroviral therapy (HAART) is able to cause lipid metabolism and glucose homeostasis alterations, which are associated to the redistribution of body fat. Alterations in lipid and carbohydrate metabolism contribute to the development of a highly atherogenic profile, which together with altered fibrinolysis markers and increased presence of proinflammatory cytokines in blood (especially tumor necrosis factor alpha) that comes associated to the success of HAART can cause the development of accelerated atherosclerosis. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid that has demonstrated its ability to reduce triglyceride levels; modify cholesterol fractions and increase the size of LDL particles thereby configuring less atherogenic plasma profile. Additionally, administration of DHA has shown antiinflammatory and hypotensive activity, which contributes to reduce the risk of cardiovascular complications in these patients. At a molecular level, DHA acts as a stimulator of the nuclear receptor PPAR-gamma, which has been described to induce an increase in adipocyte differentiation. Furthermore, the anti-inflammatory effects induced by DHA, can decrease the elevated levels of TNF-alpha, which has been implicated in the pathogenesis of body fat redistribution in HIV infected patients undergoing HAART. Therefore, the hypothesis of this project is that DHA will be able to produce lipid-lowering, anti-inflammatory, hypotensive and profibrinolytic effects, which all together should improve atherogenic profile of patients with HIV-1 infection receiving HAART. In addition, their proprieties as PPAR agonist can improve the redistribution of body fat present in many of these patients. The study of the activity of DHA on dendritic cells and monocytes should indicate the absence of immunosuppressive effect of DHA in the context of HIV-1 infection.

In summary, DHA is a natural product, from the omega 3 polyunsaturated fatty acids, the therapeutic properties of which have been described in recent years and has shown cardio-vascular and metabolic beneficial effects, without recognized side effects. The highly purified DHA administration at high doses could be able to reverse, at least partially, lipid abnormalities associated with HAART and to exert a beneficial effect on fat redistribution in HIV-infected patients treated with HAART. To ensure non deleterious immunological treat in these sensitive poly-medicated patients, substantial changes in the functionality of dendritic cells and monocytic will be studied.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Collaborators: Hospital Clinic of Barcelona; University of Barcelona

Criteria

Inclusion Criteria:

1. Serologic evidence of HIV-1.

2. Plasma triglycerides > 2.26 mmol/L (200 mg/dL) and/or Total Cholesterol > 6 mmol/L (232 mg/dL) measured after a fasting period of at least 12 hours and confirmed by at least two measures separated by at least an interval of one week.

3. Body mass index between 25 and 30 kg/m2.

4. Absence NSAIDs, antihypertensive drugs, lipid-lowering drugs treatments or any other medication known to affect plasma lipid levels.

5. Alcohol intake <20 g/day.

6. Absence of Diabetes mellitus and obesity (BMI > 30)

7. Absence of heart and liver pathologies (within 3 months prior the study).

8. Absence of renal failure (serum creatinine > 130 mmol/L) or Cr.Cl. < 60 ml/min /1.73 m2.

Exclusion Criteria:

1. Pregnancy or absence of adequate contraception in childbearing age women.

2. Presence or fail to fulfil one or more of the conditions listed in paragraphs 2-8 of the inclusion criteria