Effect of Abaloparatide on Lumbar Disc Degeneration

NCT03708926 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: IRB00185784
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Low back pain is a major public health issue as the leading cause of disability globally. Degeneration of intervertebral disc (IVD) disorder is once source of low back pain. Current treatment options for low back pain secondary to degeneration of intervertebral disc include conservative care, steroid injections, prescription pain medications, physical therapy, or surgery, such as discectomy or laminectomy. Treatments focus on addressing manifested symptoms rather than functional causes, and symptomatic treatment of discogenic low back pain is less than ideal. The investigators have recently found that parathyroid hormone (PTH) effectively attenuates disc degeneration in aged mice. This clinical trial will test if 3-months of daily PTH-related protein (PTHrP), abaloparatide will improve pain, function, and disc health in people with low back pain secondary to lumbar disc degeneration.

Conditions

Degeneration Disc Intervertebral

Keywords

degenerative disc disease; low back pain; PTH; abaloparatide

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with improvement in symptomatic or radiographic symptoms as indicated by composite score aggregated from the Oswestry Disability Index (ODI) and Pfirrmann grading system

  Composite score will be graded as a score of 0, 1 or 2, whereas: * 0 (no improvement) = less than 15 point score improvement on Oswestry Disability Index (ODI) and less than 1 grade improvement on Pfirrmann grading system. * 1 (some improvement - symptomatic or radiographic) = 15 point or greater improvement on ODI score OR at least 1 grade improvement on Pfirrmann grading system. * 2 (definite improvement) = 15 point or greater improvement on ODI score AND 1 grade or greater improvement on Pfirrmann grading system. ODI is scored on a scale of 0-100 with higher scores indicating worse disability. A decrease in ODI of 15 points is considered a clinically (symptomatic) meaningful improvement by the FDA. The modified Pfirrmann Grading system is an MRI based score (radiographic) of disc degeneration on a scale of 1-8, with higher scores indicating more severe degeneration, such that improvement is by decreasing score.

  6 months

Secondary Outcomes (11)

• Change in disability as assessed by ODI

  Baseline, 3 months, 6 months, 12 months

• Change in clinically significant improvement in disability as assessed by ODI

  Baseline, 3 months, 6 months, 12 months

• Change in pain as assessed by pain numerical rating scale

  Baseline, 3 months, 6 months, 12 months

• Change in disability as assessed by PROMIS-29 score

  Baseline, 3 months, 6 months, 12 months

• Change in radiographic markers of Degenerative Disc Disease (DDD) as assessed by absolute difference in Pfirrmann Grading system

  Baseline, 3 months, 6 months, 12 months

Study Arms (2)

abaloparatide

EXPERIMENTAL

abaloparatide 80 mcg subcutaneously once daily for 90 days

Drug: Abaloparatide

placebo

PLACEBO COMPARATOR

placebo formulated similarly but without active abaloparatide injected subcutaneously once daily for 90 days

Drug: Placebo

Interventions

Abaloparatide DRUG

abaloparatide injection pen

Also known as: Tymlos, PTHrP

abaloparatide

Placebo DRUG

placebo injection pen

placebo

Eligibility Criteria

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

You may qualify if:

• Symptomatic moderate to severe discogenic low back pain as defined by centralized chronic low back pain with a discogenic character (i.e. increases with activity, worsened with sitting or standing, or requires frequent change of positions) and has been present for 6+ months
• Identifiable change in disc morphology as defined by MRI consistent with early degenerative disc disease as defined by both Modified Pfirrmann (MRI) score of 2-3 (Graded 1-8, where 1= hydrated healthy disc, 8 = dark, dehydrated disc) and Modic Grade II change or less
• Single- or two-level DDD at lumbar spine
• \< 30% vertebral body height loss
• Oswestry disability index score \> 30
• Failed \> 3 months of appropriate non-operative care (i.e. pain medication, local drug injections, physical therapy)
• Predominant back pain with or without leg pain
• Able and willing to comply with follow-up schedule
• Willing to give written informed consent

You may not qualify if:

• Presence of objective motor deficit
• Symptomatic compressive pathology due to stenosis or disc herniation
• Any spondylolisthesis
• Any spondylolysis
• Scoliosis \> 20 degrees
• Spinal tumor
• Previous thoracic or lumbar fusion
• Current or prior fracture at T10-S1
• Arachnoiditis
• Current or prior use of PTHrP (abaloparatide) or PTH (teriparatide) analog
• Diagnosis of osteoporosis or osteopenia that is not well controlled on anti-resorptive therapy and anticipated to require use of an anabolic agent, such as abaloparatide or teriparatide.
• Evidence of metabolic bone disease as evidenced by abnormalities in calcium, intact parathyroid hormone, phosphorus or alkaline phosphatase in blood or elevated spot urine calcium to creatinine ratio.
• History of or current osteosarcoma or cancer metastatic to the bone
• History of or current Paget's disease of bone
• History of or current nephrolithiasis

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Intervertebral Disc Degeneration; Low Back Pain

Interventions

abaloparatide; Parathyroid Hormone-Related Protein

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Janet Crane, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: placebo controlled clinical trial

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 17, 2018
• Study Start: March 1, 2021
• Primary Completion: August 1, 2023
• Study Completion: February 1, 2024
• Last Updated: April 12, 2021

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)