The Efficacy of Denosumab in Incomplete Patients Spinal Cord Injury

NCT03029442 | Terminated Phase 4 DMC FDA Drug

• 1 other identifier: BAU-16-057
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the usefulness of a drug, denosumab, to prevent the loss of bone in participants legs due to SCI. This drug is FDA approved to treat osteoporosis in women after menopause who have an increased risk for fractures, to treat women receiving certain treatments for breast cancer who have an increased risk of fractures, and to treat bone loss in men receiving certain treatments for prostate cancer who have increased risk for fractures. This drug is considered experimental for the purpose of this study. Study participation will last for approximately 12 months (6 study visits total), visits will range from1-4.5 hours depending on the number of tests that need to be completed. The study is a double-blinded placebo trail in which the participant will be randomly assigned to on of two groups, Denosumab injections or placebo - inactive salt solution injections.

Conditions

Secondary Osteoporosis; Spinal Cord Injury

Keywords

Spinal Cord Injury; Denosumab; Osteoporosis; Dual Energy X-ray Absorptiometry

Outcome Measures

Primary Outcomes (1)

• areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA)

  Efficacy of denosumab to prevent aBMD loss at the distal femur and proximal tibia

  Prior to denosumab or placebo administration and 18 months after denosumab or placebo administration

Secondary Outcomes (1)

• volumetric BMD (vBMD) and microarchitecture by peripheral quantitative computed tomography

  Prior to denosumab or placebo administration and 12 months after denosumab or placebo administration

Study Arms (4)

Denosumab, AIS Grade C (non-ambulatory)

EXPERIMENTAL

8 subjects with AIS grade C will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.

Drug: Denosumab (Prolia)

Placebo, AIS Grade C (non-ambulatory)

PLACEBO COMPARATOR

8 subjects with AIS grade C will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.

Other: Placebo (normal saline)

Denosumab, AIS Grade D (ambulatory)

EXPERIMENTAL

8 subjects with AIS grade D will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.

Drug: Denosumab (Prolia)

Placebo, AIS Grade D (ambulatory)

PLACEBO COMPARATOR

8 subjects with AIS grade D will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.

Other: Placebo (normal saline)

Interventions

Denosumab (Prolia) DRUG

In clinical trials, denosumab (Amgen Inc., Thousand Oaks, CA), has been shown to be more potent in reducing osteoclastosis and function than bisphosphonates. The dose of denosumab chosen for our protocol in patients after acute SCI will be the same dose that has been shown to be efficacious to treat postmenopausal osteoporosis (60 mg SQ q 6 months).

Also known as: Xgeva

Denosumab, AIS Grade C (non-ambulatory); Denosumab, AIS Grade D (ambulatory)

Placebo (normal saline) OTHER

Identical Denosumab volume of normal saline

Placebo, AIS Grade C (non-ambulatory); Placebo, AIS Grade D (ambulatory)

Eligibility Criteria

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

You may qualify if:

• Motor incomplete SCI \[American Spinal Injury Association Impairment Scale (AIS) grades C and D\];
• Duration of injury \< 6-months; and
• Males between the ages of 18 and 65 years old and females between the ages of 18 and 50 years old.

You may not qualify if:

• Extensive life-threatening injuries in addition to SCI;
• Acute fracture or extensive bone trauma;
• History of prior bone disease (Paget's hyperparathyroidism, osteoporosis, etc.)
• Post-menopausal women;
• Men with known hypogonadism prior to SCI;
• Anabolic or Steroid hormonal therapy; within the past year and longer than six months;
• Hyperthyroidism;
• Cushing's disease or syndrome;
• Severe underlying chronic disease;
• History of chronic alcohol abuse;
• Diagnosis of Hypocalcemia;
• Pregnancy;
• Existing dental condition/dental infection;
• Diagnosis of heterotopic ossification at the hip and/or knee region and receiving a bisphosphonates \[e.g. alendronate sodium (Fosamax) or etidronate disodium (Didronel)\] that will no longer make participants eligible to receive the study medication/placebo but are still eligible to complete follow-up outcome measures as described in the work schedule;
• Current diagnosis of cancer or history of cancer; and

Sponsors & Collaborators

• James J. Peters Veterans Affairs Medical Center: lead
• Kessler Institute for Rehabilitation: collaborator

Study Sites (2)

Kessler Institute for Rehabilitation

West Orange, New Jersey, 07052, United States

Location

James J. Peters VA Medical Center

The Bronx, New York, 10468, United States

Location

Related Publications (1)

• Gifre L, Vidal J, Carrasco JL, Muxi A, Portell E, Monegal A, Guanabens N, Peris P. Denosumab increases sublesional bone mass in osteoporotic individuals with recent spinal cord injury. Osteoporos Int. 2016 Jan;27(1):405-10. doi: 10.1007/s00198-015-3333-5. Epub 2015 Sep 30.

  PMID: 26423406 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries; Osteoporosis

Interventions

Denosumab; Saline Solution

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• William A Bauman, M.D.

  James J. Peters VA Medical Center

  PRINCIPAL INVESTIGATOR

• Steven C Kirshblum, M.D.

  Kessler Institute for Rehabilitation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Clinical Investigator, National Center of Excellence for the Medical Consequences of Spinal Cord Injury

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 24, 2017
• Study Start: April 1, 2017
• Primary Completion: December 31, 2021
• Study Completion: October 6, 2022
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)