Clinical trial NCT03708926: Effect of Abaloparatide on Lumbar Disc Degeneration
Official title: Effect of Abaloparatide on Lumbar Disc Degeneration
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Degeneration Disc Intervertebral
Keywords: degenerative disc disease
low back pain
PTH
abaloparatide
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2018-10-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo controlled clinical trial
Primary purpose: TREATMENT

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.

Detailed description: The investigators will perform a randomized, double blind, placebo controlled proof-of-concept Phase 2 clinical trial of the effect of abaloparatide for the treatment of lumbar degenerative disc disease. Adults with clinically significant lumbar degenerative disc disease who meet inclusion and exclusion criteria and sign informed consent with be randomized in a 2:1 ratio to study drug:placebo.

The study team physicians will review pertinent laboratory data, medication history, and problem lists in the potential research participant's medical record to ensure eligibility for the study. The investigators will also contact the potential research participants by telephone to explain the study in further detail and elicit information not available in the medical record that would affect the potential participant's eligibility to participate in the study.

Potential research participants who meet the study criteria and are interested in participating in the study will have an appointment arranged at the Johns Hopkins Orthopedic Clinic. At the study visit, a study team physician and research coordinator will review the study and consent the research participants.

Research participants who provide informed consent will have age, sex, and ethnicity recorded, undergo a focused history and physical exam, and have any necessary blood samples collected for inclusion/exclusion criteria. The focused history will include the age of onset of symptoms, age at diagnosis of degenerative disc disease, mechanism of injury, treatments utilized, and the research participant's current perception of his or her disease control. The focused physical exam will include inspection and palpation of the affected sites to assess for pain and mobility of the spine. Research participants will be asked to rate current pain attributed to degenerative disc disease on a Likert scale pain level and asked to fill out the Oswestry Disability Index (ODI) and Patient-Reported Outcomes Measurement Information System (PROMIS-29) and have spinal x-rays and an MRI of the lumbar spine obtained.

One hundred nine people who meet the study criteria and provide informed consent will be randomly assigned to 2 groups (abaloparatide:placebo) in a 2:1 fashion (n=73 abaloparatide; 36 placebo).

Participants will be taught how to self-administer a injection of the study drug. Participants and the study doctor will not know if the participant is receiving abaloparatide or placebo as the study drug. Participants will inject the study drug daily for 3 months.

Blood and urine samples will be collected 2 weeks after study initiation to evaluate clinical safety.

Physical exams, health questionnaires, and MRI scans will be performed at 3-, 6-, and 12-month follow-up visits.

The trial will be blinded for all the investigators acquiring and analyzing the data.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* History of or current multiple myeloma
* History of focal radiation to any bone
* Current Pregnancy or breastfeeding
* Current use of medications that increase risk of hypercalcemia, such as thiazide diuretics
* Diagnosis of psychotic disorder
* Participation in another study on investigational drug
* Inability to provide informed consent

Primary outcomes:
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: Change in disability as assessed by ODI
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Change in clinically significant improvement in disability as assessed by ODI
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Change in pain as assessed by pain numerical rating scale
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Change in disability as assessed by PROMIS-29 score
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Change in radiographic markers of Degenerative Disc Disease (DDD) as assessed by absolute difference in Pfirrmann Grading system
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Change in radiographic markers of DDD as assessed by improvement in Pfirrmann Grading system
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Change in radiographic markers of DDD as assessed by average absolute difference in Modic score
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Change in radiographic markers of DDD as assessed by Modic score
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Change in pain management based on analgesic usage
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Requirement of surgical intervention for back pain by patients
timeFrame: 12 months
measure: Requirement of escalation of medical care related to back pain by patients
timeFrame: 12 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Janet Crane, M.D.
role: PRINCIPAL_INVESTIGATOR
References: