Novel Combination Therapy for Osteoporosis in Men
Osteo-Men
2 other identifiers
interventional
40
1 country
1
Brief Summary
Osteoporotic fractures are a key health problem in older men. Although there are drugs approved to treat osteoporosis in men \[bisphosphonates, denosumab, and teriparatide (TPTD) or PTH(1-34)\], there is a lack of knowledge on how to use them effectively. TPTD is a potent bone anabolic drug, meaning that it builds bone mass. However, doctors do not know if it should only be used as single drug or whether it can be more effectively combined to achieve the most benefit? This trial will test a novel combination therapy for osteoporosis in men based on exciting laboratory findings in mice. TPTD works to raise bone mass and improve bone strength by stimulating PTH receptors (PTH-Rs) on the membranes of bone-forming cells or osteoblasts (OBs). Calcimimetics are drugs that activate calcium receptors (CaSRs) in OBs. CaSRs in OBs participate in new bone formation. Daily injections of TPTD, given along with a calcimimetic drug (called NPS-R568), over 6 weeks markedly improved bone mineral density (BMD) and structure in mice. This study will test whether the combined activation of PTH-Rs and CaSRs (by the combination treatment of TPTD+calcimimetic cinacalcet) in men will produce greater bone forming responses than PTH-R activation alone (TPTD+placebo). The study has two aims and will be done in 48 men with low bone mass: (1) to determine the effects of 11 months treatment with TPTD+cinacalcet vs TPTD+placebo on BMD and bone metabolism by assessing lumbar spine BMD (primary endpoint), femoral neck BMD, and levels of the bone formation marker serum N-terminal pro-peptide of type 1 collagen; (2) to determine the biochemical responses by blood tests in men who receive the combination of TPTD+cinacalcet compared to men who get TPTD+placebo treatment. This is done by quantifying acute and chronic changes in serum calcium and PTH levels right after these drugs are given and how much calcium is excreted in the urine over time, with both treatment regimens. This study will help to understand whether an effective combination therapy in mice will prove to be effective in men.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_4
Started Jul 2019
Longer than P75 for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 18, 2019
CompletedFirst Posted
Study publicly available on registry
June 21, 2019
CompletedStudy Start
First participant enrolled
July 1, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
ExpectedJuly 31, 2025
July 1, 2025
6 years
June 18, 2019
July 30, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Effects of treatment with TPTD+cinacalcet compared to TPTD+PBO on lumbar spine BMD in men with low bone mass
Hypothesis 1a proposes that BMD responses to combined TPTD+cinacalcet are greater than those induced by TPTD+PBO. LS BMD typically responds quickly and robustly to TPTD and is the 1o endpoint of the trial. DXA measurements will be performed and analyzed by standard protocols at baseline and at the end of the trial. Subjects will be treated for 11 months (48 weeks). All subjects will receive Ca and vitamin D3 supplements throughout the trial. The percentage change in LS BMD from baseline to 48 week/11 months of treatment will be the variable/endpoint that is calculated.
48 weeks
Secondary Outcomes (2)
Effects of treatment with TPTD+cinacalcet compared to TPTD+PBO on serum P1NP in men with low bone mass
48 weeks
Effects of treatment with TPTD+cinacalcet compared to TPTD+PBO on femoral neck BMD in men with low bone mass
48 weeks
Other Outcomes (1)
Pharmacodynamic responses to TPTD+cinacalcet and to TPTD+PBO in men with low bone mass
48 weeks
Study Arms (2)
teriparatide (TPTD) + the calcimimetic cinacalcet
EXPERIMENTALCombination arm: Men randomized to this arm will take daily subcutaneous injections of teriparatide \[PTH (1-34)\] (20 mcg per day) and at the same time swallow a 30-mg tablet of cinacalcet. Men in both arms of the study will take a total of approximately 1000 mg elemental Ca through their diets and study provided Ca supplements (Ca citrate) and approximately 1000 IU vitamin D3. Men will be followed and assessed throughout the entire study using the clinical (vital signs, adverse events), laboratory (blood and urine tests) and densitometric procedures (DXA BMD and TBS) outlined in the study protocol.
teriparatide (TPTD) + placebo
PLACEBO COMPARATORMonotherapy arm: Men randomized to this arm will take daily subcutaneous injections of teriparatide \[PTH (1-34)\] (20 mcg per day) and at the same time swallow a placebo tablet. Men in both arms of the study will take a total of approximately 1000 mg elemental Ca through their diets and study provided Ca supplements (Ca citrate) and approximately 1000 IU vitamin D3. Men will be followed and assessed throughout the entire study using the clinical (vital signs, adverse events), laboratory (blood and urine tests) and densitometric procedures (DXA BMD and TBS) outlined in the study protocol.
Interventions
Teriparatide or PTH 1-34 is a 34 amino acid peptide derived by recombinant DNA technology from the authentic sequence of human parathyroid hormone. It is given by subcutaneous injection in the dosage of 20 micrograms per day in the trial in both treatment arms for the 48 weeks or 11 months of the trial.
This drug is an orally active calcimimetic (drug that activates Ca-sensing receptors on target cells) that will be given daily orally to the men randomized to the Experimental Treatment Arm (#1). Cinacalcet tablets will be given simultaneously with the injection of PTH(1-34) or teriparatide. Cinacalcet will be given only once daily but given every single day of the trial starting with the Randomization Visit for the duration of 48 weeks or 11 months of the trial.
The placebo tablet in the trial will be purchased from Consolidated Midland Corporation in Brewster, NY. Each white tablet contains Lactose, Stearic Acid and Magnesium Stearate (330 mg total). Subjects randomized to the placebo arm or Placebo - Arm #2 - will take one tablet orally at the same time as he injects the teriparatide each day. Placebo tablets will be given only once daily but given every single day of the trial starting with the Randomization Visit for the duration of 48 weeks or 11 months of the trial.
Ca citrate supplements (forms 200 or 250 mg elemental Ca/oral tablet) will be used in the study. Each subject will have average dietary Ca intake quantified by a Food Frequency Questionaire. Each subject will take sufficient Ca citrate supplements to make the total Ca intake equal \~1000 mg per day (diet+supplements). Ca supplements will be spread out during the day so that any amount of supplements over 500 mg will be taken at 2 different time-points. Ca citrate supplements will be sourced by our research pharmacist will be of high-quality and consistency. Ca supplements will be started at Screening Visit 2 and given for a 4-week run-in period. Once subjects are randomized to Arm 1 or Arm 2 of the trial, subjects will continue to take daily Ca supplements at the same dose and times as during the run-in period. That daily dosing will continue from day of Randomization through the end of 48 weeks or 11 months of the trial.
Subjects will be given 1000 IU vitamin D3 in tablet form to be taken orally once a day at any time during the day. Vitamin D3 supplements will be sourced by our research pharmacist and supplements selected for use in the trial will be of high quality and consistency. Vitamin D3 supplements will be started at Screening Visit 2 in the trial and given for a 4-week run-in period. Once subjects are randomized to Arm 1 or Arm 2 of the trial, subjects will continue to take daily vitamin D3 supplements at the same dose and timing as during the run-in period. That daily dosing will continue from the day of Randomization Visit through to the end of the 48 weeks or 11 months of the trial.
Eligibility Criteria
You may qualify if:
- DXA BMD T-score \< or = -2.0 at either lumbar spine (LS), femoral neck (FN) or total hip (TH) sites; or DXA BMD T-score \< or = -1.5 with at least one additional important clinical risk factor for osteoporotic fracture \[e.g., fragility fracture after age 50 years; parental history of hip fracture; history of hypogonadism, prior glucocorticoid therapy (\>3 months prior), current smoking, prevalent vertebral fracture(s), or prior hyperthyroidism on stable treatment\]
- At least 2 LS vertebral levels with reliable BMD values (i.e., at least 2 without compression or hardware)
You may not qualify if:
- Metabolic bone disease other than osteoporosis (e.g., Paget's disease, hyperparathyroidism)
- Any osteoporosis drug therapy within 12 months; any prior course of TPTD for \> or = 3 months; any history of IV bisphosphonate therapy; oral bisphosphonate therapy exceeding 3 months in past 2 years; oral bisphosphonate treatment exceeding 2 years ever; or use of denosumab (within the past 3 years or \> 3 or = injections ever).
- Oral glucocorticoid use (\> or = 5 mg prednisone) taken within 3 months prior to enrollment
- Hypercalcemia (albumin-corrected serum \[Ca\] \>10.2 mg/dL), hypocalcemia (albumin-corrected serum \[Ca\] \<8.8 mg/dL), elevated intact PTH level, or hypercalciuria (urinary Ca \>300 mg/24 hours) at screening
- OH vitamin D levels \<20 ng/ml or \>80 ng/ml at screening
- Estimated glomerular filtration rate \< 30 ml/min (chronic kidney disease (CKD) stage 4 or 5)
- Cancer within past 5 years except for non-melanomatous skin cancers
- History of skeletal radiation, prior history of osteosarcoma or bone metastases
- Substance abuse (\>3 drinks/day), liver disease or impaired liver function (abnormal liver function tests defined as greater than 3 times the upper limit of normal), known cirrhosis, malabsorption
- Poorly controlled diabetes (A1c \>9.0%) or current thiazolidinedione therapy
- Drugs metabolized through CYP2D6 (e.g., flecainide, tricyclic antidepressants) and strong inducers or inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole)
- Testosterone therapy with dose change within last 12 months; or androgen deprivation therapy within 12 months
- Thyrotropin (TSH) level \< 0.01
- Congenital long QT syndrome, history of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, and other conditions that predispose to QT interval prolongation and ventricular arrhythmia
- Hypersensitivity to teriparatide or any excipients in Forteo
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, 94121-1563, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dolores M. Shoback, MD
San Francisco VA Medical Center, San Francisco, CA
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- All study personnel will be masked to treatment assignment and this group will include the DXA technicians, the study coordinators, and the lab technicians and lab supervisors who will analyze samples for study results.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- FED
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 18, 2019
First Posted
June 21, 2019
Study Start
July 1, 2019
Primary Completion
June 30, 2025
Study Completion (Estimated)
June 30, 2026
Last Updated
July 31, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- Six (6) months after the trial data are published and then indefinitely afterwards
- Access Criteria
- All IDP data after deidentification collected during the trial will become available 6 months after the trial publication is published. This is a 5-year project commencing approximately July 1, 2019, and will continue through June 30, 2024, until all subject level data is collected and the trial interventions completed. Once study data are fully analyzed and published, then 6 months later, the IPD data sets and IPD Supporting Information will be available to other investigators.
Individual Participant Data (IPD) sets will be shared. All IPD collected during the trial after de-identification will be shared. The types of Supporting Information that will be shared (in addition to IDP and Data Dictionaries) include Study Protocol, Statistical Analysis Plan, Informed Consent Form, Clinical Study Report, and Analytic Code. The data will be available 6 months after the publication of the study, with no end date, and will be available to anyone who wishes to access the data and provides a methodologically sound proposal. The types of analyses that are planned in that proposal will be reviewed by the research study team of investigators, consultants and collaborators. To gain access to the data, requesting investigators will need to sign a Data Use Agreement.