Effect of Abaloparatide on Lumbar Disc Degeneration

April 7, 2021 updated by: Johns Hopkins University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: abaloparatide
abaloparatide 80 mcg subcutaneously once daily for 90 days
Drug: Abaloparatide
abaloparatide injection pen
Other Names:
  • Tymlos, PTHrP
Placebo Comparator: placebo
placebo formulated similarly but without active abaloparatide injected subcutaneously once daily for 90 days
Drug: Placebo
placebo injection pen

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: 6 months

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in disability as assessed by ODI
Time Frame: Baseline, 3 months, 6 months, 12 months
The efficacy of abaloparatide on disability will be assessed by absolute difference in ODI from baseline in abaloparatide versus placebo group, reported as average per group. ODI assessed pain related disability is scored on a scale of 0-100 with higher scores indicating worse disability.
Baseline, 3 months, 6 months, 12 months
Change in clinically significant improvement in disability as assessed by ODI
Time Frame: Baseline, 3 months, 6 months, 12 months
The efficacy of abaloparatide on disability will be assessed by percentage of patients with 15 point or greater improvement in ODI from baseline in abaloparatide versus placebo group. ODI assessed pain related disability 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 meaningful improvement by the FDA.
Baseline, 3 months, 6 months, 12 months
Change in pain as assessed by pain numerical rating scale
Time Frame: Baseline, 3 months, 6 months, 12 months
The efficacy of abaloparatide on disability will be assessed by absolute difference in pain numerical rating scale from baseline in abaloparatide versus placebo group, reported as average per group. The pain numerical rating scale assesses pain intensity on a scale of 0-10 with higher scores indicating worse pain.
Baseline, 3 months, 6 months, 12 months
Change in disability as assessed by PROMIS-29 score
Time Frame: Baseline, 3 months, 6 months, 12 months
The efficacy of abaloparatide on disability will be assessed by absolute change in PROMIS-29 score from baseline in abaloparatide versus placebo group, reported as average per group. The PROMIS-29 is a multi-dimensional quality of life instrument that assesses pain, physical function, fatigue, anxiety, depression, sleep disturbance, and social participation on a scale of 0-100 with higher scores indicating more disturbances of that dimension.
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
Time Frame: Baseline, 3 months, 6 months, 12 months
The efficacy of abaloparatide on changes in radiographic markers of DDD will be assessed by absolute difference in modified Pfirrmann Grading system from baseline, reported as average per group. The modified Pfirrmann Grading system is an MRI based score of disc degeneration on a scale of 1-8, with higher scores indicating more severe degeneration.
Baseline, 3 months, 6 months, 12 months
Change in radiographic markers of DDD as assessed by improvement in Pfirrmann Grading system
Time Frame: Baseline, 3 months, 6 months, 12 months
The efficacy of abaloparatide on radiographic markers of DDD will be evaluated using the percentage of patients with 1 grade or greater improvement in modified Pfirrmann Grading system from baseline in the abaloparatide versus placebo group. The modified Pfirrmann Grading system is an MRI based score of disc degeneration on a scale of 1-8, with higher scores indicating more severe degeneration.
Baseline, 3 months, 6 months, 12 months
Change in radiographic markers of DDD as assessed by average absolute difference in Modic score
Time Frame: Baseline, 3 months, 6 months, 12 months
The efficacy of abaloparatide on radiographic markers of DDD will be assessed by absolute difference in Modic Score from baseline, reported as average per group. Modic score is an MRI based score characterizing the vertebral endplate. Modic score correlates with progressive degenerative changes in the endplate, where 0 = normal; 1= hypervascular; 2 = fatty infiltration; 3 = sclerosis.
Baseline, 3 months, 6 months, 12 months
Change in radiographic markers of DDD as assessed by Modic score
Time Frame: Baseline, 3 months, 6 months, 12 months
The efficacy of abaloparatide on radiographic markers of DDD will be evaluated using percentage of patients with 1 grade or greater improvement in Modic Score from baseline in the abaloparatide versus placebo group. Modic score is an MRI based score characterizing the vertebral endplate. Modic score correlates with progressive degenerative changes in the endplate, where 0 = normal; 1= hypervascular; 2 = fatty infiltration; 3 = sclerosis.
Baseline, 3 months, 6 months, 12 months
Change in pain management based on analgesic usage
Time Frame: Baseline, 3 months, 6 months, 12 months
Evaluate change in pain management in abaloparatide versus placebo groups based on change in the dosage of analgesic used and the number of days of back pain (longer than 30 min/day) in week prior to baseline compared to week prior to 3-, 6-, and 12-month visits.
Baseline, 3 months, 6 months, 12 months
Requirement of surgical intervention for back pain by patients
Time Frame: 12 months
Proportion of patients proceeding to a surgical intervention within the 12-month study period in the abaloparatide versus placebo group will be assessed by percentages per arm
12 months
Requirement of escalation of medical care related to back pain by patients
Time Frame: 12 months
Proportion of patients requiring escalation of medical care related to back pain (e.g. spine surgery, injections into IVD, or Emergency Department visits related to debilitating back pain) will be assessed by percentages per arm
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Janet Crane, M.D., Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 9, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 17, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 12, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00185784

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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