Efficacy of Zoledronic Acid + Colaren vs Zoledronic Acid + Conventional Treatment for Osteoporosis in HIV+ and HIV- Men

NCT03930992 | Completed Phase 3 DMC

• 1 other identifier: OSZCO
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Clinical trial to assess the effectiveness of the supplement Colaren® associated with zoledronic acid 4mg/annually in the treatment of osteoporosis secondary, compared to standard treatment plus zoledronic acid 4mg/annually. The standard treatment will include 1gr of calcium/day and vitamin D supplement. In both cases, vitamin D levels will be determinated, which should remain at more than 30 ng/mL. Including men with osteoporosis secondary to HIV and men with osteoporosis secondary to any other cause (HIV negative). Vitamin D levels, bone densitometry and markers of metabolism, bone formation and bone resorption will be assessment. The all parameters above will be assessed basally (before the start of treatment), after starting the treatment, an assessment will be made at 12 weeks where vitamin D levels and bone markers will be measured. Meanwhile, at week 24 assess only vitamin D levels; and finally, at week 52 all parameters mentioned above will be measured.

Conditions

Secondary Osteoporosis

Keywords

4 mg zoledronic acid; Colaren; HIV; Secondary Osteoporosis; Man

Outcome Measures

Primary Outcomes (2)

• Change in Bone turnover markers (from baseline to 12 months under treatment)

  Plasma measure of (through LEGENDplex (Multiplex)): Bone formation panel that include: Osteoprotegerin (OPG) measure in pg/mL, Alkaline Phosphatase Liver/Bone/Kidney (ALPL) measure in pg/mL, LEPTINA measure in pg/mL and Bone Morphogenetic Protein 2 (BMP-2) measure in pg/mL. Bone resorption panel that include: Osteopontin (OPN) measure in pg/mL, Acid Phosphatase 5 Tartrate Resistant (ACP5) measure in pg/mL, RANKL measure in pg/mL, Tumor Necrosis Factor Alpha (TNF-α) measure in pg/mL, Interleukin 6 (IL-6) measure in pg/mL, Parathyroid Hormone (PTH) measure in pg/mL, Interleukin 1 beta (IL-1β) measure in pg/mL, Dickkopf WNT Signaling Pathway Inhibitor 1 (DKK-1) measure in pg/mL.

  Time frame: from baseline, 3 and 12 months under treatment.

• Change from baseline of Bone mineral density at 12 months

  Bone mineral density through Dual-energy X-ray absorptiometry (DXA scan) measure. Classification: Normal: T-score ≥ -1.0 Osteopenia: -2.5 \< T-score \< -1.0 Osteoporosis: T-score ≤ -2.5 Severe osteoporosis: T-score ≤ -2.5 with fragility fracture

  Time frame: from baseline and 12 months under treatment.

Secondary Outcomes (1)

• Tolerability of colaren vs standard treatment (conventional treatment): grading the severity of Adult and Pediatric Adverse Events Version 2.0

  Time frame: evaluate the tolerability from month 1, 3, 6, 9 and 12, under supplementation

Study Arms (4)

1 Arm: Experimental

EXPERIMENTAL

Experimental: 4 mg zoledronic acid plus colaren ® This arm include: 20 man with HIV infection plus osteoporosis

Drug: Colaren in HIV positive

2 Arm: Active comparator

ACTIVE COMPARATOR

Active comparator: 4mg zoledronic acid + standard treatment (or conventional treatment) This arm include: 20 man with HIV infection plus osteoporosis

Drug: standard treatment in HIV positive

3 Arm: Experimental

EXPERIMENTAL

Experimental: 4 mg zoledronic acid plus colaren ® This arm include: 20 man without HIV infection plus osteoporosis

Drug: Colaren in HIV negative

4 Arm: Active comparator

ACTIVE COMPARATOR

Active comparator: 4mg zoledronic acid + standard treatment (or conventional treatment) This arm include: 20 man without HIV infection plus osteoporosis

Drug: standard treatment in HIV negative

Interventions

Colaren in HIV positive DRUG

1 Arm (HIV+): will receive Zoledronic acid 4mg and colaren ® (vitamin D, magnesium, phosphate, calcium).

Also known as: plus Zoledronic Acid 4 mg

1 Arm: Experimental

standard treatment in HIV positive DRUG

2 Arm (HIV+): will receive Zoledronic acid 4mg and standard treatment (vitamin D and calcium carbonate)

Also known as: plus Zoledronic Acid 4 mg

2 Arm: Active comparator

Colaren in HIV negative DRUG

3 Arm (HIV-): will receive Zoledronic acid 4mg and colaren ® (vitamin D, magnesium, phosphate, calcium).

Also known as: plus Zoledronic Acid 4 mg

3 Arm: Experimental

standard treatment in HIV negative DRUG

4 Arm (HIV-): will receive Zoledronic acid 4mg and standard treatment (vitamin D and calcium carbonate)

Also known as: plus Zoledronic Acid 4 mg

4 Arm: Active comparator

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males 18 to 65 years old.
• HIV diagnosis (HIV positive group) or negative HIV serology (HIV negative group).
• Patients receiving HAART and sustained virologic control for at least two years.
• Patients meeting diagnostic criteria for osteoporosis.
• Subjects willing to participate voluntarily in this study and give a written consent.
• Estimated glomerular filtration rate \>60 mL/min (Using CKD-EPI formula).

You may not qualify if:

• Use of calcium, vitamin D or any other drug with bone activity during the last 90 days previous to the study.
• Use of herbs or herb products during the last 90 days previous to the study.
• Positive test for HCV or HBV.
• Patients who cannot be submitted to complete examination for variable analysis.
• Glomerular filtration rate \<60 mL/minute.
• Active liver disease.
• Non-compliance to treatment (less than 90%).
• Patients who are not willing to continue participating.
• Female patients.
• Use of immunosuppressive o immunomodulatory treatment 90 days previous to selection.
• Use of prohibited drugs for the study like: antiestrogens, corticosteroids (doses greater than 7.5mg of prednisone/day) 90 days previous to selection.
• Use of hormone therapy.
• Patients with history or actual use of chemotherapy.
• Patients deprived of freedom or imprisoned patients with mental illnesses.
• Participant is part of another clinical trial or nutritional program.

Sponsors & Collaborators

• University of Guadalajara: lead
• Hospital Civil de Guadalajara: collaborator

Study Sites (1)

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, 44280, Mexico

Location

Related Publications (8)

• Wheater G, Elshahaly M, Tuck SP, Datta HK, van Laar JM. The clinical utility of bone marker measurements in osteoporosis. J Transl Med. 2013 Aug 29;11:201. doi: 10.1186/1479-5876-11-201.

  PMID: 23984630 RESULT

• Sattui SE, Saag KG. Fracture mortality: associations with epidemiology and osteoporosis treatment. Nat Rev Endocrinol. 2014 Oct;10(10):592-602. doi: 10.1038/nrendo.2014.125. Epub 2014 Aug 5.

  PMID: 25091729 RESULT

• Rothman MS, Bessesen MT. HIV infection and osteoporosis: pathophysiology, diagnosis, and treatment options. Curr Osteoporos Rep. 2012 Dec;10(4):270-7. doi: 10.1007/s11914-012-0125-0.

  PMID: 23100110 RESULT

• Panayiotopoulos A, Bhat N, Bhangoo A. Bone and vitamin D metabolism in HIV. Rev Endocr Metab Disord. 2013 Jun;14(2):119-25. doi: 10.1007/s11154-013-9246-8.

  PMID: 23657562 RESULT

• Leal J, Gray AM, Prieto-Alhambra D, Arden NK, Cooper C, Javaid MK, Judge A; REFReSH study group. Impact of hip fracture on hospital care costs: a population-based study. Osteoporos Int. 2016 Feb;27(2):549-58. doi: 10.1007/s00198-015-3277-9. Epub 2015 Aug 19.

  PMID: 26286626 RESULT

• Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, Hope S, Kanis JA, McCloskey EV, Poole KES, Reid DM, Selby P, Thompson F, Thurston A, Vine N; National Osteoporosis Guideline Group (NOGG). UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. 2017 Dec;12(1):43. doi: 10.1007/s11657-017-0324-5. Epub 2017 Apr 19.

  PMID: 28425085 RESULT

• Bolland MJ, Grey AB, Horne AM, Briggs SE, Thomas MG, Ellis-Pegler RB, Woodhouse AF, Gamble GD, Reid IR. Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial. J Clin Endocrinol Metab. 2007 Apr;92(4):1283-8. doi: 10.1210/jc.2006-2216. Epub 2007 Jan 16.

  PMID: 17227801 RESULT

• Carlos F, Clark P, Maciel H, Tamayo JA. Direct costs of osteoporosis and hip fracture: an analysis for the Mexican Social Insurance Health Care System. Salud Publica Mex. 2009;51 Suppl 1:S108-13. doi: 10.1590/s0036-36342009000700014.

  PMID: 19287884 RESULT

MeSH Terms

Interventions

Seroconversion; Zoledronic Acid

Intervention Hierarchy (Ancestors)

Immune System Phenomena; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of HIV Unit in Hospital Civil de Guadalajara

Model Details: Study type: Interventional, with four arms: 1. arm: 4 mg zoledronic acid annually plus colaren ® in HIV-positive; 2. arm: 4 mg zoledronic acid annually plus conventional treatment in HIV-positive; 3. arm: 4 mg zoledronic acid annually plus colaren ® in HIV-negative; 4. arm: 4 mg zoledronic acid annually plus conventional treatment in HIV-negative.

Study Record Dates

• First Submitted: April 17, 2019
• First Posted: April 29, 2019
• Study Start: April 17, 2019
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)