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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
  Purpose

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 Intervention Phase
HIV Infection
Osteopenia
Drug: raltegravir and atazanavir and ritonavir
Drug: tenofovir/emtricitabine and atazanavir and ritonavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Turin, Italy:

Primary Outcome Measures:
  • Variations from baseline in DEXA-measured bone mineral density (t-score, spine and femur) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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


Estimated Enrollment: 66
Study Start Date: September 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01902186

Contacts
Contact: Andrea Calcagno, MD +390114393884 andrea.calcagno@unito.it

Locations
Italy
University of Milano Not yet recruiting
Milano, Italy
Contact: Stefano Rusconi, MD       stefano.rusconi@unimi.it   
Principal Investigator: Massimo Galli, MD, PhD         
Sub-Investigator: Stefano Rusconi, MD         
University of Torino Not yet recruiting
Torino, Italy
Contact: Andrea Calcagno, MD    +390114393884    andrea.calcagno@unito.it   
Sub-Investigator: Stefano Bonora, MD         
Principal Investigator: Giovanni Di Perri, MD, PhD         
Sub-Investigator: Andrea Calcagno, MD         
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

No publications provided

Responsible Party: Giovanni Di Perri, Full professor of Infectious Diseases, University of Turin, Italy
ClinicalTrials.gov Identifier: NCT01902186     History of Changes
Other Study ID Numbers: RALBAT
Study First Received: July 10, 2013
Last Updated: July 17, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University of Turin, Italy:
HIV
osteopenia
t-score
DEXA
tenofovir
raltegravir

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
HIV Seropositivity
Emtricitabine
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Atazanavir
Ritonavir
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014