Clinical trial NCT01902186: Bone Mineral Density Changes in HIV-positive Females With Osteopenia Switching to Raltegravir
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV Infection
Osteopenia
Keywords: HIV
osteopenia
t-score
DEXA
tenofovir
raltegravir
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
Collaborators: name: University of Turin, Italy
name: University of Milan
First posted: 2013-07-18
Enrollment: 4
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Variations from baseline in DEXA-measured bone mineral density (t-score, spine and femur)
timeFrame: 48 weeks
Secondary outcomes:
measure: variations from baseline in CTX (C-terminal telopeptide of type I collagen) and OC (Osteocalcin)
timeFrame: 24 and 48 weeks
measure: To assess the variation in renal function
timeFrame: 48 weeks
Other outcomes:
measure: Cholesterol changes at 48 weeks in the two arms
timeFrame: 48 weeks
measure: Triglycerides changes in the two arms
timeFrame: 48 weeks
measure: Glucose Fasting Levels changes in the two arms
timeFrame: 48 weeks
measure: Insulin changes in the two arms
timeFrame: 48 weeks
measure: Parathyroid hormone changes in the two arms
timeFrame: 48 weeks
measure: Vitamine D (25-OH-Vitamine D) changes in the two arms
timeFrame: 48 weeks
Locations:
city: Milano
country: Italy
facility: University of Milano
city: Torino
country: Italy
facility: University of Torino
Study officials:
affiliation: University of Turin, Italy
name: Giovanni Di Perri, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: