Immune Reconstitution in HIV Disease (IREHIV) (IREHIV)

Immune Reconstitution in HIV Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate

The aim with this study is to provide immunotherapy with vitamin D and phenylbutyrate to treatment-naive HIV infected patients to induce important antimicrobial defence mechanisms and decreased inflammation.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate); Drug: Placebo tablets

• Study Type: Interventional
• Enrollment (Actual): 279
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ethiopia
  • Lideta sub city
    • Addis Ababa, Lideta sub city, Ethiopia
      • Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Adult patients >18 years not subjected to HAART.

HIV-1 infected patients with CD4 T cells counts >200 cells/ml.

Detectable plasma viral loads >1000 copies/ml.

Exclusion Criteria:

Patients on HAART or other antimicrobial drugs (including bactrim).

Antimicrobial drug treatment in the past month.

Patients with medical contra-indication for biopsy such as bleeding tendencies.

Hypercalcaemia (serum calcium > 3,0 mmol/L) identified at baseline.

Pregnant and breast feeding women.

Any known liver or kidney function abnormality, malignancy or patients treated with cardiac glycosides.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo tablets; Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.	Drug: Placebo tablets; Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.
Active Comparator: Vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate); Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.	Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate); Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV viral load	Plasma HIV viral load will be used to monitor efficacy of vitamin D and phenylbutyrate treatment among treatment-naïve HIV patients at the time of diagnosis (time point 0) and at 4, 8, 16 and 24 weeks after initiation of antimicrobial treatment with vitamin D and phenylbutyrate. The primary endpoint will be assessed at 16 weeks compared to baseline (time point 0).	0 (baseline) compared to 16 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical secondary endpoints	Overall clinical symptoms. Body mass index (BMI). Mid upper arm circumference (MUAC).	0, 4, 8, 16, 24 weeks.
Laboratory secondary endpoints	HIV viral load (0, 4, 8, 24 weeks). Peripheral CD4/CD8 T cell counts. Plasma levels of vitamin D, LL-37, sCD14, LPS, 16S RNA and cytokine/chemokine profiles. Calprotectin in feces. Inflammation and microbial translocation in colon punch biopsies (0 and 16 weeks). Functional studies of immune cells (PBMCs).	0, 4, 8, 16, 24 weeks.

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Addis Ababa University; Armauer Hansen Research Institute, Ethiopia
• Investigators: Principal Investigator: Susanna Brighenti, PhD, Karolinska Institutet

Publications and helpful links

General Publications

• Missailidis C, Sorensen N, Ashenafi S, Amogne W, Kassa E, Bekele A, Getachew M, Gebreselassie N, Aseffa A, Aderaye G, Andersson J, Brighenti S, Bergman P. Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1. Nutrients. 2019 Jul 21;11(7):1675. doi: 10.3390/nu11071675.
• Ashenafi S, Amogne W, Kassa E, Gebreselassie N, Bekele A, Aseffa G, Getachew M, Aseffa A, Worku A, Hammar U, Bergman P, Aderaye G, Andersson J, Brighenti S. Daily Nutritional Supplementation with Vitamin D(3) and Phenylbutyrate to Treatment-Naive HIV Patients Tested in a Randomized Placebo-Controlled Trial. Nutrients. 2019 Jan 10;11(1):133. doi: 10.3390/nu11010133.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: September 25, 2012
• First Submitted That Met QC Criteria: October 8, 2012
• First Posted (Estimate): October 10, 2012

Study Record Updates

• Last Update Posted (Estimate): February 5, 2016
• Last Update Submitted That Met QC Criteria: February 4, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: HIV; inflammation; cholecalciferol; immune response; sodium phenylbutyrate; antimicrobial peptides
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; Antineoplastic Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; 4-phenylbutyric acid
• Other Study ID Numbers: IREHIV-2012