Folinic Acid: Supplementation and Therapy

HIV Infection Clinical Trial

— FAST  

Official title:

Effect of Folic Acid on Homocysteine Levels and Flow-mediated Dilation in HIV and HIV-HCV Coinfected Patients: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02810275
• Other study ID #: CAAE: 00533612.8.0000.5346
• Secondary ID: GPPG-140240RBR-9
• Status: Completed
• Phase: Phase 3
• First received: June 19, 2016
• Last updated: November 29, 2016
• Start date: October 2012
• Est. completion date: September 2013

Study information

• Verified date: September 2016
• Source: Hospital de Clinicas de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

Patients infected by HIV or HIV-HCV coinfected have higher survival due to the use of HAART, but survival is accompanied by increased morbidity and associated cardiovascular disease (CVD). Endothelial dysfunction is an early marker of atherogenesis, acting as an intermediate in the causal pathway of CVD. Folinic acid (FA) has been shown to reduce CVD outcomes, especially among individuals with hyperhomocisteinemia.

To date, few studies provided consistent information about efficacy of pharmacological interventions that minimize damage to the vascular endothelium in patients infected by HIV or HIV-HCV coinfected. The main hypothesis of this study is that FA supplementation protects the vascular endothelium, and consequently might prevent subclinical atherosclerosis. Thus, the first step is to determine the efficacy of supplementation with FA, and to compare the effect between HIV and HIV-HCV coinfected.

Description:

Study design: This was a randomized placebo-controlled trial, with blinding of health care team, participants, and investigators, in which the participants were randomly assigned in a 1:1 ratio to receive FA or placebo for four weeks.

Participants: Patients receiving care for HIV, at the outpatient clinic of the Hospital Universitario de Santa Maria, in southern Brazil, from October 2012 to September 2013, were recruited. Eligible participants: HIV infected or HIV-HCV coinfected patients, 18-50 years, men and women, receiving HAART, had undetectable viral load for more than six months. Patients were excluded: patients with diabetes mellitus, previous acute myocardial infarction, myocardial revascularization, or stroke, creatinine >1.5 mg/dL, clinical diagnosis or ultrasound, endoscopic, or laboratory evidence of liver cirrhosis, on treatment with statins, fibrates, hormone replacement therapy, sulfonamides, vitamin supplements, or FA in the last 30 days, and pregnant women.

Intervention Patients assigned to the intervention group received FA 5 mg, per oral, once a day, in the morning, during four weeks. Patients assigned to the placebo group received the same prescription. The trial provided FA and placebo in tablet form, identical in color, smell, taste, shape, and size. Both FA and placebo were prepared in a single batch, in an independent laboratory, by a pharmacist with no involvement in the trial. They were pre-packed in bottles containing 30 tablets each, individually labeled with an alphanumeric code and stored.

Outcomes The primary endpoint were changes in homocysteine, vitamin B12 levels, and brachial artery FMD during reactive hyperemia, as measured by Doppler ultrasound, from randomization to the end of follow-up. FMD was characterized by the variation in mean arterial flow measured as the peak change in vessel diameters relative to the baseline.

Sample size Sample size was calculated based on the results of a previous RCT,(14) which used plethysmography to measure FMD. To detect a difference of at least 6% between intervention and placebo groups, with standard deviations ranging from 5% to 7%, we calculated that a sample size of at least 17 patients per group, with randomization stratified by HCV coinfection status, was required to achieve 80% power and a 95% confidence interval.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: September 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion criteria:

• HIV infected patients

• HIV-HCV coinfected patients

• 18-50 years

• men and women

• receiving HAART

• with undetectable viral load for more than six months.

Exclusion Criteria:

• Patients with diabetes mellitus,

• previous CVD: acute myocardial infarction, myocardial revascularization, or stroke,

• creatinine >1.5 mg/dL,

• clinical diagnosis or ultrasound, endoscopic, or laboratory evidence of liver cirrhosis,

• on treatment with: statins, fibrates, hormone replacement therapy, sulfonamides, vitamin supplements, or FA in the last 30 days,

• pregnant women.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coinfection
• HCV Coinfection
• HIV Infection
• HIV Infections

Intervention

Drug:
• Folinic Acid
Folinic acid 5 mg, taking in the morning, daily, during four weeks
• Placebo
Placebo capsule received 1 tablet, taking in the morning, during four weeks

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre	Universidade Federal de Santa Maria

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood pressure	The response was defined by variation in blood pressure between intervention and placebo groups.	Four weeks	No
Primary	Flow mediated dilatation	The response was defined by the variation in the flow mediated dilatation between intervention and placebo groups.	Four weeks	No
Secondary	Serum homocysteine	Variation in the serum homocysteine between intervention and placebo groups.	Four weeks	No