Antiretroviral Therapy Intensification With Raltegravir or Addition of Hyper-immune Bovine Colostrum in HIV-1 Infected Patients With Suboptimal CD4+ T Cell Response (CORAL)

• ClinicalTrials.gov Identifier: NCT00772590
• Recruitment Status: Completed
• First Posted: October 15, 2008
• Results First Posted: August 24, 2012
• Last Update Posted: August 24, 2012
• Sponsor: Kirby Institute
• Information provided by (Responsible Party): Kirby Institute

Study Description

Brief Summary:

A research study to measure the effect on CD4 counts of adding to current anti-retroviral regimen raltegravir with or without hyper-immune bovine colostrum.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: Raltegravir; Drug: Hyper-immune Bovine Colostrum; Other: raltegravir placebo; Other: Hyper-immune Bovine Colostrum placebo; Drug: raltegravir and hyper-immune bovine colostrum	Phase 4

Detailed Description:

The primary objective of this study is to measure the effect on CD4+ T cell outcome as measured by the mean time weighted CD4+ T cell count change over 24 weeks of two interventions: (I) cART intensification with raltegravir and (II) cART combined with hyper-immune bovine colostrum in HIV-1 infected individuals who have failed to achieve a CD4+ T cell count greater than 350 cells/µL despite persistent HIV plasma viraemia below 50 copies/mL on cART.

Eligible patients will be randomised to one of four arms. I. Raltegravir + hyper-immune bovine colostrum placebo II. Raltegravir placebo + hyper-immune bovine colostrum III. Raltegravir + hyper-immune bovine colostrum IV. Raltegravir placebo + hyper-immune bovine colostrum placebo

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomised Double-blind Placebo Controlled Study to Measure the Effect of Antiretroviral Therapy (ART) Intensification With Raltegravir and/or Hyper-immune Bovine Colostrum on CD4+ T Cell Count in ART Treated, HIV-1 Infected Individuals With Suboptimal CD4+ T Cell Responses
• Study Start Date: March 2009
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: June 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Raltegravir, bovine colostrum; Raltegravir and hyper-immune bovine colostrum	Drug: raltegravir and hyper-immune bovine colostrum; 400mg twice daily raltegravir and 1800mg twice daily of hyper-immune bovine colostrum; Other Name: Raltegravir + hyper-immune bovine colostrum
Experimental: Hyper-immune bovine colostrum; Hyper-immune bovine colostrum and Raltegravir placebo	Drug: Hyper-immune Bovine Colostrum; Tablet, 1800mg, twice daily
Experimental: Raltegravir; Raltegravir and Hyper-immune Bovine Colostrum Placebo	Drug: Raltegravir; Tablets, 400mg, twice daily
Placebo Comparator: Placebo; Raltegravir placebo and hyper-immune bovine colostrum placebo	Other: raltegravir placebo; One tablet, twice daily; Other Name: placebo; Other: Hyper-immune Bovine Colostrum placebo; Three tablets twice daily

Outcome Measures

Primary Outcome Measures :

1. Mean Change From Baseline CD4+ Cell Count [ Time Frame: 24 weeks ]
   Comparison of normalised mean change from baseline CD4+ cell count

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Documented HIV-1 infection
• Age >18 years
• Signed informed consent
• Receiving combination ART (cART) for at least 12 months with a stable cART regimen for a minimum of 6 months. A formulation change or modification of dosage schedule is acceptable (for example ritonavir - boosted lopinavir capsules for tablets, abacavir (ABC) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC) as single agents for ABC/3TC or TDF/FTC fixed dose combinations)
• Two consecutive plasma HIV RNA viral load measurements <50 (or <400 copies/mL depending upon lowest level of detection of the local assay) in the 9 months preceding the screening visit. A single isolated HIV RNA viral load >50 (or >400) copies/mL will not exclude the patient provided the viral load result >50 (or 400) copies/mL on therapy follows a previous result <50 (or 400) copies/mL, and there is a follow-up result <50 copies/mL at least one week following the >50 (or 400) copies/mL reading in the absence of a change to any component of the ART regimen.
• CD4+ T cell count <350 cells/µL throughout the 6 months preceding the screening visit with <50 cells/µL increase in the last 12 months

Exclusion Criteria:

• Receiving a cART regimen containing an integrase inhibitor
• Anticipated change of cART in the 24 weeks following randomisation
• Participating in study with an investigational compound or device within 30 days of signing informed consent
• Use of immune modulating therapies or immunosuppressive medications within 60 days prior to study entry. Patients using inhaled or nasal steroids are not excluded
• Pregnant or breastfeeding woman
• Cow's milk allergy
• Concurrent treatment with phenobarbitol, phenytoin or rifampicin.
• A known cause of impaired CD4+ T cell gain: for example, patients with splenomegaly or individuals whose current cART regimen contains both tenofovir and didanosine

Contacts and Locations

Sponsors and Collaborators

Kirby Institute

Investigators

• Principal Investigator: Sean Emery, BSc (Hons), PhD; National Centre in HIV Epidemiology and Clinical Research, University of New South Wales

More Information

Publications of Results:

Byakwaga H, Kelly M, Purcell DF, French MA, Amin J, Lewin SR, Haskelberg H, Kelleher AD, Garsia R, Boyd MA, Cooper DA, Emery S; CORAL Study Group. Intensification of antiretroviral therapy with raltegravir or addition of hyperimmune bovine colostrum in HIV-infected patients with suboptimal CD4+ T-cell response: a randomized controlled trial. J Infect Dis. 2011 Nov 15;204(10):1532-40. doi: 10.1093/infdis/jir559. Epub 2011 Sep 19.

• Responsible Party: Kirby Institute
• ClinicalTrials.gov Identifier: NCT00772590
• Other Study ID Numbers: NCHECR-CORAL 1
• First Posted: October 15, 2008
• Results First Posted: August 24, 2012
• Last Update Posted: August 24, 2012
• Last Verified: July 2012

Keywords provided by Kirby Institute:

HIV; antiretroviral therapy intensification; suboptimal CD4+ T cell response; virological suppression; bovine colostrum; raltegravir

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Raltegravir Potassium; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action