Efficacy of Intradiscal Injection of Autologous BM-MSC in Worker Patients Affected by Chronic LBP Due to Multilevel IDD

NCT04759105 | Completed Phase 2 DMC

• 2 other identifiers: ACTIVE trial_(BRIC2018-ID03)2019-004476-19
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

ACTIVE is a phase II B efficacy monocenter, prospective, randomized, controlled double blinded trial, in which intra-discal autologous adult BM-MSC therapy will be compared with sham treated controls. This trial will evaluate the efficacy of intradiscal injection of autologous BM-MSCs in workers affected by chronic low back pain (LBP) unresponsive to conventional therapy. The efficacy will be evaluated 12 months after the treatment in terms of pain relief (VAS, Visual Analog Scale), functionality (ODI, Oswestry Disability Index), quality of life (SF36, Short Form - 36) and work ability index (WAI).

Conditions

Intervertebral Disc Degeneration; Chronic Low-back Pain

Keywords

Low back pain; Spine; Intervertebral disc degeneration; Mesenchymal stem cells; Bone marrow

Outcome Measures

Primary Outcomes (3)

• Pain clinical relief

  Pain clinical reduction of at least 40 percent on Visual Analogic Scale (VAS) between baseline and month 12. VAS pain scale ranges from 0 to 100, where 0 represents no pain and 100 represents the worst pain imaginable.

  Baseline to month 12

• Functional disability index improvement

  Functional disability reduction of 40 percent on Oswestry Disability Index (ODI, also known as the Oswestry Low Back Pain Disability Questionnaire) at month 12 compared with baseline. ODI scale ranges from 0 to 50 and allows evaluation of disability (0 - 20 percent: minimal disability; 20 - 40 percent: moderate disability; 40 - 60 percent: severe disability; 60 - 80 percent: crippled; 80 - 100 percent: bed-bound or exaggerating their symptoms).

  Baseline to month 12

• Work ability improvement

  Improvement of 10 percent on Work Ability Index (WAI) at month 12 compared to baseline. The WAI is composed of 7 items and is a validated instrument that assesses the individual work ability of an employee. The total WAI score ranges from 7 to 49 and is calculated by summing up the scores of the 7 items.

  Baseline to month 12

Secondary Outcomes (11)

• Measure pain relief of the patient

  Baseline, 1, 3 and 6 months

• Measure functional disability index of the patient

  Baseline, 1, 3 and 6 months

• Evaluate disability and quality of life evolution of the patient

  Baseline, 1, 3, 6 and 12 months

• Disability and quality of life evolution

  Baseline, 1, 3, 6 and 12 months

• Assess rescue painkillers medication

  Baseline, 1, 3, 6 and 12 months

Study Arms (2)

Autologous BM-MSC injection

EXPERIMENTAL

Two interventions: * Bone marrow harvesting from the posterior superior iliac crest region * Single injections of a dose of 15 million of autologous BM-MSC each disc affected by IDD (up to 4 discs) via imaging control

Drug: Autologous BM-MSC

Sham Procedure

SHAM COMPARATOR

Two sham procedures: * Simulated bone marrow harvesting without insertion into the posterior iliac crest region * Simulated injection under only local anaesthesia without disc injection, without placebo injection.

Other: Sham Procedure

Interventions

Autologous BM-MSC DRUG

intradiscal injection of autologous bone marrow mesenchymal stromal/stem cells

Also known as: Treated

Autologous BM-MSC injection

Sham Procedure OTHER

anaesthesia, no disc injection, no placebo injection

Also known as: Sham

Sham Procedure

Eligibility Criteria

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

You may qualify if:

• Workers (it means subject has worked at least 2 months, even if not continuously, in the last 6 months)
• Age between 18 and 65 years.
• Signed informed consent.
• Symptomatic chronic LBP due to moderate/severe IDD \[modified Pfirrmann score 3-5 (Pfirrmann et al., 2001), Griffith score 4-8 (Griffith et al., 2007)\] at max. 4 levels of the lumbar spine unresponsive to conservative treatment, physical and medical for at least 6 months. Physical treatment includes physiotherapy. Medical treatments includes AINS, paracetamol, opioids and myorelaxant.
• Annulus fibrosus intact, demonstrated by MRI.
• Pain baseline \> 40 mm on VAS (0- 100).
• NSAID washout of at least 2 days before screening.
• Painkillers washout of at least 24 hours before screening.
• For females of childbearing potential, a negative pregnancy test must be documented at Screening.
• Men and women should use effective contraception during treatment and for at least 12 months after BM-MSC discontinuation. The complete list of contraceptive methods is described in the patient information sheet and in the paragraph 6.5. As a precautionary measure, breast-feeding should be discontinued during treatment with BM-MSC and should not be restarted after discontinuation of BM-MSC.

You may not qualify if:

• Non-workers (it means that the person has worked less than 2 months, although not continuously, in the last 6 months)
• Congenital or acquired diseases leading to spine deformations that may upset cell application (scoliosis, isthmus lesion, sacralization and hemisacralization, degenerative spondilolisthesis).
• Spinal segmental instability assessed by dynamic X-Ray.
• Symptomatic facet joints syndrome on MRI (facet joints hyperintensity and hypertrophy evaluated at coronal T2 weighted MRI).
• Prior to the screening visit, has received:
• Oral corticosteroid therapy within the previous 3 months, OR
• Intramuscular, intravenous or epidural corticosteroid therapy within the previous 3 months
• Presence of a 5th level with symptomatic IDD (modified Pfirrmann score 3-5, Griffith score 4-8) in the lumbar spine.
• Spinal canal stenosis (Schizas score \> B).
• History of spinal infection.
• Lumbar disc herniation and sciatica.
• Endplate abnormality such as Schmorl's Nodes.
• Previous discal puncture or previous spine surgery.
• IDD with Modic III changes on MRI images.
• Patients not eligible to the intravertebral disc surgery.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Campus Bio-Medico: lead
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator
• Center for Outcomes Research and Clinical Epidemiology, Italy: collaborator

Study Sites (1)

Campus Bio-Medico University of Rome

Roma, 00128, Italy

Location

MeSH Terms

Conditions

Intervertebral Disc Degeneration; Low Back Pain

Interventions

Therapeutics; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

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

Study Officials

• Gianluca Vadalà, MD, PhD

  Campus Bio-Medico University of Rome

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The randomization result will be a treatment code. The treatment code of the patient will be transmitted to local pharmacy. Blinding or masking will be carried out at all stages of packaging and conditioning for shipping following the treatment allocation. Injections used for all groups will be clear and indistinguishable from each other.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Model Details: Patients will be randomized in 2 arms of 26 patients and followed up for 12 months.

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 18, 2021
• Study Start: November 3, 2019
• Primary Completion: November 27, 2023
• Study Completion: November 27, 2023
• Last Updated: May 25, 2025

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)