Micronutrients and Antioxidants in HIV Infection

HIV Infection Clinical Trial

— MAINTAIN  

Official title:

A Randomized Control Clinical Trial Of Micronutrient & Antioxidant Supplementation in Persons With Untreated HIV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00798772
• Other study ID #: CTN 238
• Status: Completed
• Phase: N/A
• First received: November 25, 2008
• Last updated: April 13, 2018
• Start date: January 2009
• Est. completion date: December 6, 2017

Study information

• Verified date: April 2018
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Infection with human immunodeficiency virus (HIV) causes decline in immunity or the ability to fight infection and progresses to acquired immunodeficiency disease (AIDS). Anti-HIV drug treatment has improved the prognosis of persons with HIV infection, but is expensive and potentially toxic. Low micronutrient levels occur in the blood even in early stages of HIV infection and increase risk of a poorer prognosis, but the role of micronutrient and antioxidant supplements in medical management of HIV/AIDS is not well defined. The proposed clinical trial aims to assess if supplementation of untreated HIV-infected adults with a micronutrient and antioxidant preparation can delay decline in immunity or disease progression or start of anti-HIV drug treatment compared with supplementation with standard multivitamins. If the findings are positive, the study has implications for health and health care savings.

Description:

Background: Antiretroviral therapy (ART) has improved the prognosis of persons with human immunodeficiency virus (HIV) infection, but is expensive and potentially toxic. Micronutrient deficiencies occur even in early stages of HIV infection and increase risk of morbidity, disease progression to acquired immunodeficiency syndrome (AIDS) and mortality, but the role of micronutrient antioxidant supplements in medical management of HIV/AIDS is not clear.

Objective: To determine if supplementation of untreated asymptomatic HIV-infected persons with a broad-spectrum micronutrient and antioxidant preparation will reduce the rate of decline of CD4 T lymphocyte count, or delay emergence of documented CDC-defined AIDS-defining illness, or start of ART compared to 100% recommended daily allowance (RDA) multivitamins and minerals, and is safe.

Study design: A prospective, randomized, controlled, double blind clinical trial of supplementation of 218 untreated asymptomatic HIV-infected adults with a micronutrient and antioxidant preparation or identical appearing RDA multivitamins and minerals for two years, with quarterly follow up in clinic for assessment of time from baseline to CD4 count <350 mm3, or emergence of documented CDC-defined AIDS-defining illness, or start of ART.

Participants and sample size: 218 participants from clinics in Ontario and other participating centres of the CIHR Canadian HIV Trials Network (CTN).

Study duration: approximately five years, allowing for approximately three years for participant accrual and two years follow-up.

Eligibility criteria: The main eligibility criteria are:

• Asymptomatic HIV-infected adults at least 18 years of age

• CD4+ cells ≥375 and ≤750 cells/mm3

• No previous ART (excluding less than seven days and perinatal transmission prophylaxis) Study intervention: Oral supplementation with a broad spectrum micronutrient and antioxidant preparation (n=109) or identical appearing RDA multivitamins and minerals (n=109).

Primary outcome: Time from baseline to CD4+ cell count <350 cells/mm3 (confirmed by two measures at least one week apart), or emergence of documented CDC-defined AIDS-defining illness, or start of ART

Secondary outcomes:

• Non-AIDS related adverse events

• Tolerance of and adherence to study medication

• Time from baseline to CD4+ cell count <350 cells/mm3 (confirmed by two measures at least one week apart)

• Time from baseline to emergence of documented CDC-defined AIDS-defining illness

• Time from baseline to start of ART

• Serial quarterly lymphocyte measures: absolute lymphocyte count (ALC), CD4+, CD8+, and CD3+ cell counts, CD4%, CD8%, CD4:CD8

• Serial quarterly HIV RNA plasma viral load

• Serum chemistries: Glucose, BUN, creatinine, total protein, C-reactive protein, albumin, alkaline phosphatase, ALT, AST, total bilirubin

• Serum micronutrient levels: Carotene (quarterly) and vitamin B12 (quarterly), folate (six monthly) and vitamin D (25-OHD, six monthly)

• Quality of Life measures: MOS HIV, EuroQol, and Health Utilities Index (HUI) Statistical analysis: Analysis of the primary outcome by intention-to-treat will compare time from baseline to primary outcome. Interim analyses are planned once 100 participants are followed for one year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 171
• Est. completion date: December 6, 2017
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• be an asymptomatic HIV infected adult

• at least 18 years of age

• have CD4+ cells between 375 and 750 cells/mm3

• have received no ART (excluding less than seven days and perinatal transmission prophylaxis)

• if a woman of child bearing potential, have a negative pregnancy test within two weeks prior to randomization and agree to practice barrier method of birth control during the study

• be willing and able to sign informed consent and to comply with the study protocol

Exclusion Criteria:

• have HIV-2 infection alone

• have known allergy or intolerance to any study medication ingredient

• be pregnant

• have active treatment for an acute opportunistic infection or malignancy

• have ALT greater than 3 x normal range

• have known cirrhosis of the liver

• have serum creatinine less than 133 umol/L

• abuse alcohol and recreational drugs

• be taking micronutrient (except vitamin D*) or natural health product supplements within 30 days of randomization *Maximum 2000 IU daily (Health Canada Guidelines).

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infection
• HIV Infections
• Infection

Intervention

Dietary Supplement:
• Micronutrients and antioxidants
8 capsules twice daily for two years
• Multivitamins and minerals
8 capsules twice daily for two years

Locations

Country	Name	City	State
Canada	The Ottawa Hospital, General Campus	Ottawa	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	CIHR Canadian HIV Trials Network, Ontario HIV Treatment Network

Country where clinical trial is conducted

Canada, 

References & Publications (2)

Austin J, Singhal N, Voigt R, Smaill F, Gill MJ, Walmsley S, Salit I, Gilmour J, Schlech WF 3rd, Choudhri S, Rachlis A, Cohen J, Trottier S, Toma E, Phillips P, Ford PM, Woods R, Singer J, Zarowny DP, Cameron DW; CTN 091/CRIT Cartenoids Study Group. A community randomized controlled clinical trial of mixed carotenoids and micronutrient supplementation of patients with acquired immunodeficiency syndrome. Eur J Clin Nutr. 2006 Nov;60(11):1266-76. Epub 2006 May 24. — View Citation

Kaiser JD, Campa AM, Ondercin JP, Leoung GS, Pless RF, Baum MK. Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: a prospective, double-blinded, placebo-controlled trial. J Acquir Immune Defic Syndr. 2006 Aug 15;42(5):523-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time from baseline to CD4+ cell count <350 cells/mm3 (confirmed by two measures at least one week apart), or emergence of documented CDC-defined AIDS-defining illness, or start of ART		Quarterly
Secondary	Non-AIDS related adverse events		Quarterly
Secondary	Tolerance of and adherence to study medication		Quarterly
Secondary	Time from baseline to CD4+ cell count <350 cells/mm3 (confirmed by two measures at least one week apart)		Quarterly
Secondary	Time from baseline to emergence of documented CDC-defined AIDS-defining illness		Quarterly
Secondary	Time from baseline to start of ART		Quarterly
Secondary	Serial quarterly lymphocyte measures (ALC, CD4+, CD8+, and CD3+ cell counts, CD4%, CD8%, CD4:CD8)		Quarterly
Secondary	Serial quarterly HIV RNA plasma viral load		Quarterly
Secondary	Serum chemistries: Glucose, BUN, creatinine, total protein, albumin, alkaline phosphatase, ALT, AST, total bilirubin,		Quarterly
Secondary	Serum micronutrient levels: carotene (quarterly), vitamin B12 (quarterly), folate (six monthly) and vitamin D (25-OHD six monthly)		Quarterly or as specified
Secondary	Quality of Life measures		Quarterly