Bone Mineral Density Changes in HIV-positive Females With Osteopenia Switching to Raltegravir (RALBAT)

• ClinicalTrials.gov Identifier: NCT01902186
• Recruitment Status: Terminated
• First Posted: July 18, 2013
• Last Update Posted: October 17, 2018
• Sponsor: Giovanni Di Perri
• Collaborators: University of Turin, Italy; University of Milan
• Information provided by (Responsible Party): Giovanni Di Perri, University of Turin, Italy

Study Description

Brief Summary:

Given the high prevalence of bone alteration in the course of HIV infection or antiretroviral treatment and the favourable properties of raltegravir the investigators designed this pilot randomized and controlled study. Adult female HIV-positive patients on successful treatment with tenofovir/emtricitabine plus atazanavir plus ritonavir will be randomized either to continue such a regimen or to switch to raltegravir plus atazanavir plus ritonavir. Bone mineral density changes will be compared in the two groups at 48 weeks: the hypothesis is that removing tenofovir and using tenofovir will increase bone mineral density at 48 weeks.

Condition or disease	Intervention/treatment	Phase
HIV Infection; Osteopenia	Drug: raltegravir and atazanavir and ritonavir; Drug: tenofovir/emtricitabine and atazanavir and ritonavir	Phase 4

Detailed Description:

The objective is to assess the improvement in Bone Mineral Density and markers of bone turnover in women on TDF/FTC (tenofovir disoproxil fumarate/ emtricitabine)+ ATV/r (atazanavir/ritonavir) in a switch arm (RAL (raltegravir) + ATV/r) vs. an unchanged arm (TDF/FTC + ATV/r).

The clinical hypothesis is that removing tenofovir (associated to a boosted PI, and therefore in the worst clinical scenario) in both pre-menopausal and menopausal women could be beneficial and being associated with reduced bone mineral density loss measured by DEXA (densitometry)scan scores and markers of bone turnover. The underlying mechanism is believed to be the reduction in hyper-phosphaturia induced by proximal tubular dysfunction: therefore measuring renal tubular markers and hormones involved in calcium and phosphorus homeostasis (such as vitamin D and parathormone) will explain the suspected mechanism.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Switching HIV-positive Women on Tenofovir/Emtricitabine Plus Boosted Atazanavir to RALtegravir Plus Boosted ATazanavir: A Pilot Randomized Clinical Trial Investigating 48-weeks Changes in Bone Mineral Density
• Study Start Date: September 2014
• Actual Primary Completion Date: December 2016
• Actual Study Completion Date: December 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: raltegravir; raltegravir and atazanavir and ritonavir	Drug: raltegravir and atazanavir and ritonavir; switch tenofovir/emtricitabine to raltegravir; Other Names: Isentress (raltegravir); Reyataz (atazanavir); Norvir (ritonavir)
Active Comparator: tenofovir/emtricitabine; tenofovir/emtricitabine and atazanavir and ritonavir	Drug: tenofovir/emtricitabine and atazanavir and ritonavir; no change in antiretroviral treatment; patients will continue their regimen (tenofovir/emtricitabine and atazanavir and ritonavir); Other Names: tenofovir/emtricitabine (Truvada); atazanavir (Reyataz); ritonavir (norvir)

Outcome Measures

Primary Outcome Measures :

1. Variations from baseline in DEXA-measured bone mineral density (t-score, spine and femur) [ Time Frame: 48 weeks ]

Secondary Outcome Measures :

1. variations from baseline in CTX (C-terminal telopeptide of type I collagen) and OC (Osteocalcin) [ Time Frame: 24 and 48 weeks ]
2. To assess the variation in renal function [ Time Frame: 48 weeks ]
   glomerular filtration rate, urinary markers of tubular dysfunction (nondiabetic glucosuria, altered resorption of phosphorus, hyperaminoaciduria, b2-micro-globuline excretion and abnormal uric acid excretion.) and urinary retinol binding protein

Other Outcome Measures:

1. Cholesterol changes at 48 weeks in the two arms [ Time Frame: 48 weeks ]
   Changes in Cholesterol levels in the two arms
2. Triglycerides changes in the two arms [ Time Frame: 48 weeks ]
   Changes in Tryglicerdies levels in the two arms
3. Glucose Fasting Levels changes in the two arms [ Time Frame: 48 weeks ]
   Changes in Glucose Fasting Levels in the two arms
4. Insulin changes in the two arms [ Time Frame: 48 weeks ]
   Changes in Insulin levels in the two arms
5. Parathyroid hormone changes in the two arms [ Time Frame: 48 weeks ]
   Changes in Parathyroid hormone levels in the two arms
6. Vitamine D (25-OH-Vitamine D) changes in the two arms [ Time Frame: 48 weeks ]
   Changes in Vitamine D (25-OH-Vitamine D)levels in the two arms

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adult HIV-positive female patients;
• osteopenia (t-score from -1 to -2.5);
• On antiretroviral treatment with tenofovir/emtricitabine and atazanavir/ritonavir (300/100 mg) for at least six months;
• Plasma HIV RNA below 50 copies/ml since six months;
• Premenopausal women: female patients at any phase of the reproductive period with regular menstrual cycles and normal FSH (< 25 ng/mL) That would probably exclude patients with ovarian or endocrinological dysfunctions. Pre and postmenopausal should be therefore well-characterized.
• Women in menopausal period (the menopause was defined as 12 months of amenorrhoea without any pathological or physiological cause and using the endocrinological definition of ovary insufficiency (LH (Luteic hormone) >25ng/mL, FSH (follicule stimulating hormone)>25ng/mL and E2 (Estradiol)<30ng/mL).
• Each premenopausal sexually active subject of child-bearing potential must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for 3 months after stopping the medication.Medically accepted methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD (intrauterine device), inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation).
• Postmenopausal women are not required to use contraception.

Exclusion Criteria:

• History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
• Documented resistance to Raltegravir or/and Atazanavir.
• Patient with significant hypersensitivity or other contraindication to any of the components of the study drugs.
• Patient has a current (active) diagnosis of acute hepatitis due to any cause
• Patient with coinfection HIV/HBV (Human Hepatitis virus B)
• Liver cirrhosis
• Osteoporosis (t-score less than 2.5).
• Secondary endocrinological cause of low BMD (Bone mineral density)
• Chronic steroid intake;
• Chronic kidney disease (estimated glomerular filtration rate below 60 ml/min);
• Concomitant use of bisphosphonate.

Contacts and Locations

Locations

Italy

University of Milano

Milano, Italy

University of Torino

Torino, Italy

Sponsors and Collaborators

Giovanni Di Perri

University of Turin, Italy

University of Milan

Investigators

• Principal Investigator: Giovanni Di Perri, MD, PhD; University of Turin, Italy

More Information

• Responsible Party: Giovanni Di Perri, Full professor of Infectious Diseases, University of Turin, Italy
• ClinicalTrials.gov Identifier: NCT01902186
• Other Study ID Numbers: RALBAT
• First Posted: July 18, 2013
• Last Update Posted: October 17, 2018
• Last Verified: October 2018

Keywords provided by Giovanni Di Perri, University of Turin, Italy:

HIV; osteopenia; t-score; DEXA; tenofovir; raltegravir

Additional relevant MeSH terms:

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Ritonavir; Atazanavir Sulfate; Tenofovir; Emtricitabine; Raltegravir Potassium; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors