Ignite Creation Date:
2024-05-06 @ 1:14 AM
Last Modification Date:
2024-10-26 @ 11:01 AM
Study NCT ID:
NCT01768182
Status:
COMPLETED
Last Update Posted:
2013-01-25
First Post:
2013-01-02
Brief Title:
Folinic Acid and Vascular Reactivity in HIV
Sponsor:
Hospital de Clinicas de Porto Alegre
Organization:
Hospital de Clinicas de Porto Alegre
Study Overview
Official Title:
Short-term Folinic Acid Supplementation Improves Vascular Reactivity in HIV-infected Individuals a Randomized Trial
Status:
COMPLETED
Status Verified Date:
2013-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Objective HIV infected individuals present a cluster of conditions that activate or injure the vascular endothelium The administration of folates may exert beneficial effects on endothelial function in different populations at risk for cardiovascular disease The aim of the study was to determine the effects of 4 weeks folinic acid supplementation on forearm vascular responses during reactive hyperemia in HIV-infected people under antiretroviral therapy
Methods This was a prospective randomized double-blind placebo-controlled trial to compare the effects of 4 weeks daily ingestion of 5 mg folinic acid n15 or placebo n15 Participants had to be on anti-retroviral therapy for at least 6 months before enrollment with undetectable viral load and CD4 cell count 200 cellsmm3 Vascular function was evaluated with venous occlusion plethysmography at baseline and after 4 weeks for the determination of brachial artery reactive hyperemia and after isosorbide dinitrate administration
Methods This was a prospective randomized double-blind placebo-controlled trial to compare the effects of 4 weeks daily ingestion of 5 mg folinic acid n15 or placebo n15 Participants had to be on anti-retroviral therapy for at least 6 months before enrollment with undetectable viral load and CD4 cell count 200 cellsmm3 Vascular function was evaluated with venous occlusion plethysmography at baseline and after 4 weeks for the determination of brachial artery reactive hyperemia and after isosorbide dinitrate administration
Detailed Description:
Design and participants This was a randomized double-blind placebo-controlled trial Eligible participants were individuals with known HIV disease according to Centers for Disease Control revised criteria aged 18 or over on ART for at least 6 months with undetectable viral load less than 50 copiesml and CD4 counts more than 200 cellsmm3 Exclusion criteria were diabetes mellitus any active infection liver disease renal disease history of cardiovascular disease or uncontrolled hypertension pregnancy use of illicit drug and mental illness that would compromise understanding and collaboration with the study Patients currently using tobacco taking any dietary supplement such as folic acid or antioxidants or women taking hormone replacement therapy were also excluded All medications in regular use were maintained throughout the study period The protocol was approved by the committee for ethics in research of the Hospital de Clínicas de Porto Alegre and all participants gave written informed consent
Study settings The study took place at the HIV outpatient clinic of the Hospital de Clínicas de Porto Alegre a national reference center for HIVAIDS in southern Brazil from August 2009 to September 2011
Interventions Participants were randomly assigned to a 4-week treatment with either folinic acid n15 or placebo n15 The study supplementation regimens consisted of the capsules containing 5 mg of folinic acid or placebo Participants were provided with 1 bottle which contained 30 capsules Subjects were instructed to take 1 capsule daily in the morning
Outcomes The primary outcome measure was assessment of brachial artery vascular responses during reactive hyperemia Secondary outcomes were the changes on the biochemical and hemodynamic variables
Vascular measurements After an overnight fast the assessments were performed in a temperature-controlled 20-22C quiet room with subjects in the supine position Throughout the protocol blood pressure BP and heart rate were measured in the dominant arm using a calibrated oscillometric automatic device Dinamap 1846 SXP Critikon Florida USA Forearm blood flow was measured by venous occlusion plethysmography DE Hokanson Washington USA in the nondominant limb as previously described In short a rapid inflator cuff was used in the upper arm to occlude venous outflow and hand circulation was arrested by placing a cuff around the wrist Reactive hyperemia RH was induced by placing a cuff in the upper-arm at 250 mmHg and releasing after 5 min All flow recordings were manually traced by an operator who was blinded to the groups and time The reproducibility of flow measurements in our laboratory has intraday and interday coefficients of variation of 69 and 92 respectively After 15 min of rest 25 mg of sublingual isosorbide dinitrate Isordil Sigma Brazil was administered as an endothelium-independent vasodilator Five minutes later endothelium-independent vasodilatation of the brachial artery was measured
Laboratory measurements All samples were obtained after an overnight fast before and after 4 weeks of intervention For each subject total plasma homocysteine concentration serum folate vitamin B12 glucose creatinine total cholesterol high density lipoprotein cholesterol HDL-C and triglycerides were measured Serum folate and vitamin B12 levels were measured by a competitive immunoassay using direct chemiluminescent technology Bayer ADVIA Centaur Leverkusen Germany Plasma homocysteine levels were also measured by a competitive immunoassay using direct chemiluminescent technology IMMULITE 2000 Siemens Illinois USA Glucose creatinine total cholesterol HDL-c and triglycerides were measured with standard laboratory methods
Sample size and randomization Power calculations showed that a total number of 15 participants per group would be able to detect a change of 4mlmin100ml in vascular response during reactive hyperemia between groups with a power of 80 and α005 For allocation of the participants randomization was achieved by computer-generated list of random numbers and the investigators remained blind until the study was completed Participants were randomly assigned to placebo or folinic acid treatment groups The randomization procedure was performed in three blocks of 10 and was stratified according to sex to ensure a relatively equal number of men and women in each treatment group
Folinic acid and placebo capsules were indistinguishable in shape size as well as color They were pre-packed in identical bottles and consecutively numbered for each patient according to the randomization schedule Supplements were coded so that neither the investigators nor the participants were aware of the contents A person not affiliated with the study was the only one entrusted with the identification code for the individually wrapped bottles of capsules
Statistical analysis All variables were tested for normal distribution with the Kolmogorov-Smirnov test Normally distributed variables are expressed as mean SEM Variables non-normally distributed are presented as median 25th-75th percentiles Baseline comparisons of group characteristics were carried out by unpaired t-test or Mann-Whitney U test To compare responses after 4 weeks of intervention a two-way analysis of variance ANOVA for repeated measures group time and interaction was used Associations between changes in serum folic acid and changes in RH and associations between changes in plasma homocysteine and changes in RH were evaluated by Spearmans rank correlation coefficient A two-tailed P value of less than 005 was considered as statistically significant
Study settings The study took place at the HIV outpatient clinic of the Hospital de Clínicas de Porto Alegre a national reference center for HIVAIDS in southern Brazil from August 2009 to September 2011
Interventions Participants were randomly assigned to a 4-week treatment with either folinic acid n15 or placebo n15 The study supplementation regimens consisted of the capsules containing 5 mg of folinic acid or placebo Participants were provided with 1 bottle which contained 30 capsules Subjects were instructed to take 1 capsule daily in the morning
Outcomes The primary outcome measure was assessment of brachial artery vascular responses during reactive hyperemia Secondary outcomes were the changes on the biochemical and hemodynamic variables
Vascular measurements After an overnight fast the assessments were performed in a temperature-controlled 20-22C quiet room with subjects in the supine position Throughout the protocol blood pressure BP and heart rate were measured in the dominant arm using a calibrated oscillometric automatic device Dinamap 1846 SXP Critikon Florida USA Forearm blood flow was measured by venous occlusion plethysmography DE Hokanson Washington USA in the nondominant limb as previously described In short a rapid inflator cuff was used in the upper arm to occlude venous outflow and hand circulation was arrested by placing a cuff around the wrist Reactive hyperemia RH was induced by placing a cuff in the upper-arm at 250 mmHg and releasing after 5 min All flow recordings were manually traced by an operator who was blinded to the groups and time The reproducibility of flow measurements in our laboratory has intraday and interday coefficients of variation of 69 and 92 respectively After 15 min of rest 25 mg of sublingual isosorbide dinitrate Isordil Sigma Brazil was administered as an endothelium-independent vasodilator Five minutes later endothelium-independent vasodilatation of the brachial artery was measured
Laboratory measurements All samples were obtained after an overnight fast before and after 4 weeks of intervention For each subject total plasma homocysteine concentration serum folate vitamin B12 glucose creatinine total cholesterol high density lipoprotein cholesterol HDL-C and triglycerides were measured Serum folate and vitamin B12 levels were measured by a competitive immunoassay using direct chemiluminescent technology Bayer ADVIA Centaur Leverkusen Germany Plasma homocysteine levels were also measured by a competitive immunoassay using direct chemiluminescent technology IMMULITE 2000 Siemens Illinois USA Glucose creatinine total cholesterol HDL-c and triglycerides were measured with standard laboratory methods
Sample size and randomization Power calculations showed that a total number of 15 participants per group would be able to detect a change of 4mlmin100ml in vascular response during reactive hyperemia between groups with a power of 80 and α005 For allocation of the participants randomization was achieved by computer-generated list of random numbers and the investigators remained blind until the study was completed Participants were randomly assigned to placebo or folinic acid treatment groups The randomization procedure was performed in three blocks of 10 and was stratified according to sex to ensure a relatively equal number of men and women in each treatment group
Folinic acid and placebo capsules were indistinguishable in shape size as well as color They were pre-packed in identical bottles and consecutively numbered for each patient according to the randomization schedule Supplements were coded so that neither the investigators nor the participants were aware of the contents A person not affiliated with the study was the only one entrusted with the identification code for the individually wrapped bottles of capsules
Statistical analysis All variables were tested for normal distribution with the Kolmogorov-Smirnov test Normally distributed variables are expressed as mean SEM Variables non-normally distributed are presented as median 25th-75th percentiles Baseline comparisons of group characteristics were carried out by unpaired t-test or Mann-Whitney U test To compare responses after 4 weeks of intervention a two-way analysis of variance ANOVA for repeated measures group time and interaction was used Associations between changes in serum folic acid and changes in RH and associations between changes in plasma homocysteine and changes in RH were evaluated by Spearmans rank correlation coefficient A two-tailed P value of less than 005 was considered as statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None