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

Study Overview
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Brief Summary
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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.

Detailed Description
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This study is a clinical trial to assess the effectiveness of the supplement Colaren® associated with annually zoledronic acid 4mg, in the treatment of osteoporosis secondary or not to HIV infection, 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 evaluated, 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.

Official Title
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Efficacy of 4 mg Zoledronic Acid Plus Colaren vs 4mg Zoledronic Acid + Conventional Treatment for Secondary Osteoporosis in HIV Positive and Negative Men

Conditions
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Secondary Osteoporosis

Intervention / Treatment
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* Drug: Colaren in HIV positive
* Drug: standard treatment in HIV positive
* Drug: Colaren in HIV negative
* Drug: standard treatment in HIV negative


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Exclusion Criteria: 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. Non-inclusion criteria: 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. Hypogonadism diagnosis with not having received hormonal replacement previous to the study. Primary osteoporosis diagnosis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study type: Interventional, with four arms: arm: 4 mg zoledronic acid annually plus colaren ® in HIV-positive; arm: 4 mg zoledronic acid annually plus conventional treatment in HIV-positive; arm: 4 mg zoledronic acid annually plus colaren ® in HIV-negative; arm: 4 mg zoledronic acid annually plus conventional treatment in HIV-negative.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Arm: Experimental<br>Experimental: 4 mg zoledronic acid plus colaren ® This arm include: 20 man with HIV infection plus osteoporosis | Drug: Colaren in HIV positive<br>* 1 Arm (HIV+): will receive Zoledronic acid 4mg and colaren ® (vitamin D, magnesium, phosphate, calcium).<br>* Other names: plus Zoledronic Acid 4 mg;|
| Active Comparator: 2 Arm: Active comparator<br>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<br>* 2 Arm (HIV+): will receive Zoledronic acid 4mg and standard treatment (vitamin D and calcium carbonate)<br>* Other names: plus Zoledronic Acid 4 mg;|
| Experimental: 3 Arm: Experimental<br>Experimental: 4 mg zoledronic acid plus colaren ® This arm include: 20 man without HIV infection plus osteoporosis | Drug: Colaren in HIV negative<br>* 3 Arm (HIV-): will receive Zoledronic acid 4mg and colaren ® (vitamin D, magnesium, phosphate, calcium).<br>* Other names: plus Zoledronic Acid 4 mg;|
| Active Comparator: 4 Arm: Active comparator<br>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<br>* 4 Arm (HIV-): will receive Zoledronic acid 4mg and standard treatment (vitamin D and calcium carbonate)<br>* Other names: plus Zoledronic Acid 4 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of colaren vs standard treatment (conventional treatment): grading the severity of Adult and Pediatric Adverse Events Version 2.0 | Evaluation of tolerability of Colaren and conventional treatment through the Division of AIDS table for grading the severity of Adult and Pediatric Adverse Events Version 2.0, November 2014 Grade 1= Mild Grade 2= Moderate Grade 3= Severe Grade 4= Potentially | Time frame: evaluate the tolerability from month 1, 3, 6, 9 and 12, under supplementation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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4 mg zoledronic acid, Colaren, HIV, Secondary Osteoporosis, Man