Back to resultsA Study to Evaluate Efficacy and Safety of Denosumab for Prevention and Treatment of Osteoporosis in 1st Time Liver Transplant Recipients.
Primary Purpose
Osteoporosis
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Denosumab Injection
Placebos
Sponsored by
About this trial
This is an interventional prevention trial for Osteoporosis
Eligibility Criteria
Inclusion Criteria:
- Age >=18 years old
- First-time Liver transplant Recipients
- All men, postmenopausal women and women with history of hysterectomy or tubal ligation
- Patients who have not been treated with medications for Osteoporosis within the past 12 months before the liver transplant
- Patients able and agreeable to follow up at out Institution for the duration of the study
- Patients hospitalized for less than 45 consecutive days after the liver transplant surgery
- Patients with GFR>30ml/min (calculated by Cockcroft-Gault equation, see Table 3 for details)
- Patients with corrected Calcium >= 8.5
- Patients with PTH intact levels WNL (as per lab values)
- Patients with vit D>=20; NOTE: patients with vit D <20 will be treated with high dose Ergocalciferol 50,000 units daily and rechecked in 2 weeks
- Patients with t-score >=-3.5 at all sites checked by DEXA scan
- Patients agree to sign an informed consent form to be in the study
- Can be treated with denosumab or placebo within 3 months from the liver transplant date
Exclusion Criteria:
- Patients with previous transplants
- Patients that are getting 2 simultaneous transplants, like combined kidney and liver transplants
- Age < 18 year old
- Patients hospitalized for over 45 days after the liver transplant surgery
- Patients with GFR< 30ml/min
- Patients with hypocalcemia defined as corrected calcium < 8.5
- Patients with extensive dental problems, previous hx of Osteonecrosis of the jaw (ONJ) and/or high risk for developing ONJ
- Patients with current Hyperthyroidism
- Patients with current Primary Hyperparathyroidism defined by the combination of elevated calcium and PTH intact levels
- Patients with severe Osteoporosis as defined by t-score <-3.5 at any site shown by DEXA scan
- Women of reproductive age without history of tubal ligation or hysterectomy
- Patients who cannot read or understand the Informed Consent Document or study instructions
- Patients with diagnosis of dementia, or otherwise unable to give informed consent
- Patients unable to follow up in our Institution for the duration of the study
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Denosumab receiving group.
Placebo receiving group.
Arm Description
Patients in this arm will receive denosumab injection 60 mg subcutaneously every 6 months. (A total of 4 injections)
Patients in this arm will receive Placebo injection subcutaneously every 6 months. (A total of 4 injections)
Outcomes
Primary Outcome Measures
The percentage changes in bone mass calculated by DEXA scan t-score of Lumbar Spine in the intervention and control groups at 12 months.
Secondary Outcome Measures
The percentage changes in bone mass calculated by DEXA scan t-score of Femoral Neck, Total Hip and Wrist in the intervention and control groups at 12 months.
The percentage changes in bone mass calculated by DEXA scan t-score of Lumbar Spine, Femoral Neck, Total Hip and Wrist in the intervention and control groups at 24 months.
The vertebral and non-vertebral fracture incidence at 12 and 24 months.
The percentage changes of biochemical markers of variables of bone turnover (BSAP, CTX and PINP) from baseline to 6, 12, 18 and 24 months after 1st medication administration.
The percentage changes of creatinine, Calcium, Magnesium, Phosphorus, PTH intact and 25-Vit D levels from baseline to 6, 12, 18 and 24 months after the 1st medication administration.
The percentage of patients developing infections, rejection episodes, hospitalizations or ED visits during the study period.
Full Information
NCT ID
NCT04231682
First Posted
January 3, 2020
Last Updated
June 24, 2020
Sponsor
Albert Einstein Healthcare Network
Collaborators
Amgen
1. Study Identification
Unique Protocol Identification Number
NCT04231682
Brief Title
A Study to Evaluate Efficacy and Safety of Denosumab for Prevention and Treatment of Osteoporosis in 1st Time Liver Transplant Recipients.
Official Title
A Prospective Randomized Double-Blind, Placebo-Controlled Phase 2 Study Evaluating the Efficacy and Safety of Early Administration of Denosumab 60mg for Prevention and Treatment of Osteoporosis in First-time Liver Transplant Recipients
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Grant support was withdrawn from Amgen Pharmaceuticals
Study Start Date
July 1, 2020 (Anticipated)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Albert Einstein Healthcare Network
Collaborators
Amgen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
Organ transplant recipients are known to suffer from bone loss and subsequent fractures after the transplant operation with the most rapid bone loss occurring within the first 3-12 months. Guidelines for prevention and treatment of this serious complication are only written by individual medical societies interested in each organ (separate kidney from liver or heart transplants management) and they are based on studies done with limited medications choices. The majority of studies are done with the use of bisphosphonates, and there are very limited, or no data, on the effect of other medications used for Osteoporosis, including the use of denosumab. This study will focus on the evaluation of the efficacy and safety of denosumab 60mg use early (within first 3 months) after Liver Transplantation in the management of bone loss and prevention of fragility fractures. Different tests will be used to study the effect of the medication on the skeleton, including imaging studies as well as specific labwork.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Denosumab receiving group.
Arm Type
Experimental
Arm Description
Patients in this arm will receive denosumab injection 60 mg subcutaneously every 6 months. (A total of 4 injections)
Arm Title
Placebo receiving group.
Arm Type
Placebo Comparator
Arm Description
Patients in this arm will receive Placebo injection subcutaneously every 6 months. (A total of 4 injections)
Intervention Type
Drug
Intervention Name(s)
Denosumab Injection
Intervention Description
Use of denosumab in post liver transplant patient for prevention and management of osteoporosis and bone loss.
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Use of placebo in post liver transplant patient for prevention and management of osteoporosis and bone loss.
Primary Outcome Measure Information:
Title
The percentage changes in bone mass calculated by DEXA scan t-score of Lumbar Spine in the intervention and control groups at 12 months.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
The percentage changes in bone mass calculated by DEXA scan t-score of Femoral Neck, Total Hip and Wrist in the intervention and control groups at 12 months.
Time Frame
12 months
Title
The percentage changes in bone mass calculated by DEXA scan t-score of Lumbar Spine, Femoral Neck, Total Hip and Wrist in the intervention and control groups at 24 months.
Time Frame
24 months
Title
The vertebral and non-vertebral fracture incidence at 12 and 24 months.
Time Frame
12 and 24 months
Title
The percentage changes of biochemical markers of variables of bone turnover (BSAP, CTX and PINP) from baseline to 6, 12, 18 and 24 months after 1st medication administration.
Time Frame
6, 12, 18 and 24 months
Title
The percentage changes of creatinine, Calcium, Magnesium, Phosphorus, PTH intact and 25-Vit D levels from baseline to 6, 12, 18 and 24 months after the 1st medication administration.
Time Frame
6, 12, 18 and 24 months
Title
The percentage of patients developing infections, rejection episodes, hospitalizations or ED visits during the study period.
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >=18 years old
First-time Liver transplant Recipients
All men, postmenopausal women and women with history of hysterectomy or tubal ligation
Patients who have not been treated with medications for Osteoporosis within the past 12 months before the liver transplant
Patients able and agreeable to follow up at out Institution for the duration of the study
Patients hospitalized for less than 45 consecutive days after the liver transplant surgery
Patients with GFR>30ml/min (calculated by Cockcroft-Gault equation, see Table 3 for details)
Patients with corrected Calcium >= 8.5
Patients with PTH intact levels WNL (as per lab values)
Patients with vit D>=20; NOTE: patients with vit D <20 will be treated with high dose Ergocalciferol 50,000 units daily and rechecked in 2 weeks
Patients with t-score >=-3.5 at all sites checked by DEXA scan
Patients agree to sign an informed consent form to be in the study
Can be treated with denosumab or placebo within 3 months from the liver transplant date
Exclusion Criteria:
Patients with previous transplants
Patients that are getting 2 simultaneous transplants, like combined kidney and liver transplants
Age < 18 year old
Patients hospitalized for over 45 days after the liver transplant surgery
Patients with GFR< 30ml/min
Patients with hypocalcemia defined as corrected calcium < 8.5
Patients with extensive dental problems, previous hx of Osteonecrosis of the jaw (ONJ) and/or high risk for developing ONJ
Patients with current Hyperthyroidism
Patients with current Primary Hyperparathyroidism defined by the combination of elevated calcium and PTH intact levels
Patients with severe Osteoporosis as defined by t-score <-3.5 at any site shown by DEXA scan
Women of reproductive age without history of tubal ligation or hysterectomy
Patients who cannot read or understand the Informed Consent Document or study instructions
Patients with diagnosis of dementia, or otherwise unable to give informed consent
Patients unable to follow up in our Institution for the duration of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Anastasopoulou, MD, PhD
Organizational Affiliation
Einstein Medical Center Philadelphia.
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Evaluate Efficacy and Safety of Denosumab for Prevention and Treatment of Osteoporosis in 1st Time Liver Transplant Recipients.
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