Injection of an Autologous A2M Concentrate Alleviates Back Pain in FAC-positive Patients

Intradiscal Injection of an Autologous Alpha-2-macroglobulin (A2M) Concentrate Alleviates Back Pain in FAC-positive Patients

A cartilage degradation product, the Fibronectin-Aggrecan complex (FAC), has been identified in patients with degenerative disc disease (DDD). Alpha-2-macroglobulin (A2M) can prevent the formation of the G3 domain of aggrecan, reducing the fibronectin-aggrecan G3 complex and therefore may be an efficacious treatment. The present study was designed to determine 1) the ability of autologous concentrated A2M to relieve back pain in patients with LBP from DDD and 2) the ability of FAC to predict the response to this biologic therapy.

24 patients with low back pain and MRI-concordant DDD had prospective evaluation. Oswestry disability index (ODI) and visual analog scores (VAS) were noted at baseline and at 3- and 6-month follow-up. Primary outcome of clinical improvement was defined as patients with both a decrease in VAS of at least 3 points and ODI >20 points. Molecular discography and delayed FAC analysis and injection of platelet poor plasma at the time of the procedure. Patients with FACT-positive assays were significantly more likely to show improvement in their VAS and ODI at follow-up.

Study Overview

• Status: Completed
• Conditions: Low Back Pain
• Intervention / Treatment: Other: autologous PPP injection

Detailed Description

Objectives: A cartilage degradation product, the Fibronectin-Aggrecan complex (FAC), has been identified in patients with degenerative disc disease (DDD). Alpha-2-macroglobulin (A2M) can prevent the formation of the G3 domain of aggrecan, reducing the fibronectin-aggrecan G3 complex and therefore may be an efficacious treatment. The present study was designed to determine 1) the ability of autologous platelet poor plasma (PPP) with concentrated A2M to relieve back pain in patients with low back pain (LBP) from DDD and 2) the ability of FAC to predict the response to this biologic therapy.

Study design/setting: Prospective cohort

Patients: 24 patients with low back pain and MRI-concordant DDD

Methods: All patients underwent lavage for molecular discography and delayed FAC analysis and injection of autologous platelet poor plasma (PPP) rich in A2M (Cytonics Autologous Protease Inhibitor Concentrate, APIC) at the time of the procedure. ANOVA with Bonferonni correction for multiple comparisons was performed.

• Study Type: Observational
• Enrollment (Actual): 24

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with LBP

Description

Inclusion Criteria:

• 18 years of age or greater with a history of low back pain complaints primarily dictated by pain with associated sensory symptoms and/or low back pain for 6 months or more who had failed expectant management with NSAIDS, activity modification, and/or physical therapy.
• MRI that demonstrated signs of degenerative disc disease at one or more levels with a Pfirrmann grade of II to IV.
• Age from 18 to 65 with axial back pain of at least 6 months duration.

Exclusion Criteria:

• Patients with a history of oral or injected corticosteroid medication within a three month period prior to disc injection.
• Chronic medical conditions associated with metabolic or inflammatory disorders (insulin-dependent diabetes mellitus, severe coronary artery disease, rheumatic or autoimmune diseases) were excluded from the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
groups that are fac + and -; autologous PPP injection is given to all patients. Prior to injection, a lavage of the disc space is taken to test for FAC.	Other: autologous PPP injection; autologous platelet poor plasma (PPP) injection taken from the participants own blood is injected in to all patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oswestry Disability Index (ODI)	Change from Baseline ODI at 3 and 6 months	3 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Score (VAS)	Change from Baseline VAS at 3 and 6 months	3 and 6 month

Collaborators and Investigators

• Sponsor: Scuderi, Gaetano J., M.D.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: June 24, 2016
• First Submitted That Met QC Criteria: October 11, 2017
• First Posted (ACTUAL): October 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2017
• Last Update Submitted That Met QC Criteria: October 11, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: back pain; FAC; biologic,; Alpha 2 Macroglobulin; A2M; APIC; FACT
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain
• Other Study ID Numbers: 201601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO