Zoledronic Acid for the Prevention of TDF-sparing ART-induced Bone Mass Density Loss in Treatment-naive HIV Positive Individuals

A Single Dose Intravenous Administration of Zoledronic Acid for the Prevention of TDF-sparing ART-induced Bone Mass Density Loss in Treatment-naive HIV Positive Individuals - a Prospective, Multicenter, Open-label, Randomized Control Trial

The goal of this clinical trial is to learn if zolendric acid can prevent the anticipated deterioration of bone mass after antiviral treatment initiation for people that were recently diagnosed with HIV.

The main questions it aims to answer are:

1. Is bone mass deterioration is significant even with the new medication currently used to treat HIV?
2. Can one dose of Zolendric acid protect from deterioration of bone mass.

Researchers will compare one dose of zolendric acid to follow-up only

Participant will:

1. Provide blood samples for bone markers before antiviral treatment initiation and at 6M,12M,24M and 48M after treatment initiation
2. Perform DXA scan soon after antiviral treatment initiation and after 12M ,24 M and 48 months
3. Half of the patients with moderate reduction in bone mass will be treated with one dose of zolendric acid in the clinical trial, the other participants will be followed without intervention.
4. Patients with substantial osteoporosis will be treated according to standard of care by their HMO, but will continue followup in the study.

Study Overview

• Status: Recruiting
• Conditions: Osteopenia; HIV Infected Individuals
• Intervention / Treatment: Drug: Zoledronic Acid 5 mg/Bag 100 ml Inj

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hila Doctor Elinav, Doctor; Phone Number: +972587874340; Email: hilaelinav@gmail.com
• Study Contact Backup: Name: Auryan Szalat, Doctor; Phone Number: +9725078743735; Email: auryans@hadassah.org.il

Study Locations

• Israel
  • Haifa, Israel
    • Not yet recruiting
    • Rambam Medical Center
    • Contact: Eynat Kedem, Doctor; Phone Number: 972536283187; Email: e_kedem@rambam.health.gov.il
    • Principal Investigator: Eynat Kedem, Doctor
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Hebrew University Medical Center
    • Contact: Hila Elinav, Doctor; Phone Number: +972587874340; Email: hilaelinav@gmail.com
    • Contact: Daniella Iluz; Phone Number: 972504048807; Email: danielaI@hadassah.org.il
    • Principal Investigator: Hila Elinav, Doctor
    • Sub-Investigator: Auryan Szalat, Doctor
    • Sub-Investigator: Shalev Lussheimer, Doctor
    • Sub-Investigator: Keren Olshtain-pops, Doctor
    • Sub-Investigator: Sarah Israel, Doctor
    • Sub-Investigator: 'Yonatan Oster, Doctor
    • Sub-Investigator: Maya Korem, Doctor
    • Sub-Investigator: Daniel Grupel, Doctor
    • Sub-Investigator: Efrat Orenbuch-Harroch, Doctor
  • Ramat Gan, Israel
    • Not yet recruiting
    • Sheba Medical Center
    • Contact: Itzchak Levy, Preoffesor; Phone Number: 972526667525; Email: itsik.levi@sheba.health.gov.il
    • Sub-Investigator: Itzchak Levy, Proffesor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults over age of 18 years old of any gender, social, religious or racial background.
• Confirmed positive result for HIV infection.

Exclusion Criteria:

Patients who received previous pharmacological agents for the prevention of HIV infection.

• Women who are pregnant, lactating or those who plan to become pregnant within the trial timeframe.
• Past history of severe drug-induced reaction (including atypical femur fractures or osteonecrosis of the jaw) or documented hypersensitivity to a bisphosphanate agent.
• Patients with untreated hypocalcemia at screening.
• Severe dental status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zoledronic acid; Patients with T score from -1 to -2.4 will be treated with 1 dose of 5 mg of Zoledronic acid within a month of ART intiation.	Drug: Zoledronic Acid 5 mg/Bag 100 ml Inj; Zolendric acid will be provided to HIV naïve patients with documented osteopnia
No Intervention: Follow up-comparator; Patients with T score from -1 to -2.4 that will be followed without intervention
No Intervention: mildly osteopenic patients; patients with T score more than -1 will be followed only after antiviral treatment initiation- P1NP and CTX levels and DXA up to 4 years
No Intervention: Osteoporotic patients; patients with T score less than -2.5 will be treated according to standard of care with oral biphosphonates, and will be followed after antiviral treatment intiation- P1NP + CTX and DXA up to 4 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone density at 12 months.	Average change (in %) from baseline in spine T score and hip T-score values among participants in the intervention group versus participants in the control group at 12 months after ART initiation	12 months of initiation of ART

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone density at 48 months.	Average change (in %) from baseline in spine- and hip T-score values among participants in the intervention group versus participants in the control group at 48 months of initiation of ART.	48 months of initiation of ART
Bone fractures at 48 months	To estimate the rates of clinical fractures among all participants over a minimum of 48 months and the difference, if any, between treatment arms.	48 months of initiation of ART
Bone markers differences during folloe up	Identify difference in average blood levels of bone turnover markers between treatment arm and the non intervention arm during the follow-up period.	6,12,24,48 months after treatment intiation
BMD decline in TDF sparing ART	Rates of BMD decline (by means of rate of naïve PLHIV with baseline T score > -1.0 who will turn to T score <-1.0) in PLHIV treated with TDF-sparing ART over a period of 48 months.	48 months of initiation of ART
Bone density at 24 months.	Average change (in %) from baseline in spine T score and hip T-score values among participants in the intervention group versus participants in the control group at 24. ART.	24 months

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Collaborators: Sheba Medical Center; Rambam Hospital, Haifa, Israel
• Investigators: Principal Investigator: Hila Elinav, Doctor, Hadassah University Medical Center; Principal Investigator: Eynat Kedem, Doctor, Rambam Health Care Campus; Principal Investigator: Itzchak Levy, Proffesor, Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: December 31, 2024
• First Submitted That Met QC Criteria: January 6, 2025
• First Posted (Actual): January 8, 2025

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 13, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Osteopenia; zoledronic acid; HIV naïve
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Diseases, Metabolic; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Organophosphorus Compounds; Organophosphonates; Diphosphonates; Zoledronic Acid
• Other Study ID Numbers: 012724-HMO-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No