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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2013 by University of Turin, Italy
Sponsor:
Collaborators:
University of Turin, Italy
University of Milan
Information provided by (Responsible Party):
Giovanni Di Perri, University of Turin, Italy
ClinicalTrials.gov Identifier:
NCT01902186
First received: July 10, 2013
Last updated: July 17, 2013
Last verified: July 2013

July 10, 2013
July 17, 2013
September 2013
March 2015   (final data collection date for primary outcome measure)
Variations from baseline in DEXA-measured bone mineral density (t-score, spine and femur) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01902186 on ClinicalTrials.gov Archive Site
  • variations from baseline in CTX (C-terminal telopeptide of type I collagen) and OC (Osteocalcin) [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • To assess the variation in renal function [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    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
Same as current
  • Cholesterol changes at 48 weeks in the two arms [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Changes in Cholesterol levels in the two arms
  • Triglycerides changes in the two arms [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Changes in Tryglicerdies levels in the two arms
  • Glucose Fasting Levels changes in the two arms [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Changes in Glucose Fasting Levels in the two arms
  • Insulin changes in the two arms [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Changes in Insulin levels in the two arms
  • Parathyroid hormone changes in the two arms [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Changes in Parathyroid hormone levels in the two arms
  • Vitamine D (25-OH-Vitamine D) changes in the two arms [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Changes in Vitamine D (25-OH-Vitamine D)levels in the two arms
Same as current
 
Bone Mineral Density Changes in HIV-positive Females With Osteopenia Switching to Raltegravir
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

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infection
  • Osteopenia
  • Drug: raltegravir and atazanavir and ritonavir
    switch tenofovir/emtricitabine to raltegravir
    Other Names:
    • Isentress (raltegravir)
    • Reyataz (atazanavir)
    • Norvir (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)
  • Experimental: raltegravir
    raltegravir and atazanavir and ritonavir
    Intervention: Drug: raltegravir and atazanavir and ritonavir
  • Active Comparator: tenofovir/emtricitabine
    tenofovir/emtricitabine and atazanavir and ritonavir
    Intervention: Drug: tenofovir/emtricitabine and atazanavir and ritonavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
66
September 2015
March 2015   (final data collection date for primary outcome measure)

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.
Female
18 Years to 80 Years
No
Contact: Andrea Calcagno, MD +390114393884 andrea.calcagno@unito.it
Italy
 
NCT01902186
RALBAT
No
Giovanni Di Perri, University of Turin, Italy
Giovanni Di Perri
  • University of Turin, Italy
  • University of Milan
Principal Investigator: Giovanni Di Perri, MD, PhD University of Turin, Italy
University of Turin, Italy
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP