First-in-human Pilot Study for the Safety Assessment of DXM Gel in Patients With Painful Lumbar Degenerative Disc Disease
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Degenerative Disc Disease
- Sponsor
- Gelmetix
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- The number of patients with at least one adverse event (AE) or serious adverse event (SAE)
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to assess the safety and the efficacy of an hydrogel (double cross-link microgel - DXM) injection into the intervertebral disc (IVD) space in patients with painful lumbar degenerative disc disease (DDD) over 24 to 48 weeks.
Detailed Description
After being informed of the study and the potential risks, all patients matching the eligibility criteria and who have given their written consent will undergo a gel injection at day 0 after a period of screening of up to 14 days. Then, they will be followed-up for a variable period according to the cohort : * first cohort of 5 patients with only one disc to be treated will be followed during 48 weeks, * second cohort of 5 patients with 2 discs to be treated will be followed during 36 weeks, * third cohort of 10 patients with 1 or 2 discs to be treated will be followed during 24 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patient aged between 18 and 55 (inclusive)
- •Discogenic low back pain, confirmed by a history of Low Back Pain, with a minimum of 3 months of continuous pain or 6 months of acute episodes of pain despite the conservative treatment including painkillers and physiotherapy
- •Oswestry Disability Index (ODI) ≥ 30% and ≤ 60%,
- •Painful disc(s) between L1 and S1 represented
- •For cohort 1L: at a single disc level
- •For cohort 2L: at 2 disc levels
- •For cohort 1-2L: at 1 or 2 disc levels
- •Patients with a Zung depression score ≤ 49, Note: Patients with a Zung depression score between ≥ 50 and ≤ 64 may be included if deemed suitable for trial inclusion by the investigator
- •Partial dehydration (grey disc) confirmed by MRI, grade II/III Pfirrmann classification
- •Pfirrmann Grade I lesions are not contra-indications to recruitment, but can never be the target of any intervention in this trial. Patients featuring grade I disc(s) in conjunction with a grade II/III meet the inclusion criteria for his(her) disc Grade II/III disc to be treated
Exclusion Criteria
- •Averted nerve root pain and potential root compression Note: Referred leg pain authorised
- •Presence of posterior bone spurs (osteophytes)
- •Partial or total Modic signal grade 1 at the considered disc level
- •Patients with active systemic infection or infection localized to the site of the proposed implantation.
- •Any conditions not described in the indications for use.
- •Any mental conditions or neuromuscular disease that may generate an unacceptable risk of failure or postoperative complication.
- •Patients with existing disc herniation at the considered level and on adjacent discs
- •Endplate disease, defect or weakness, e.g. Schmorl nodule
- •Vertebral bone abnormalities with active angioma
- •Disc collapse ≥ 15% when disc height is compared to the height of the upper adjacent disc
Outcomes
Primary Outcomes
The number of patients with at least one adverse event (AE) or serious adverse event (SAE)
Time Frame: Between screening visit and 24 weeks (measured at each visits)
An adverse event (AE) is any untoward medical occurrence in a patient exposed to a medical device and which does not necessarily have a causal relationship with this medical device. An AE can therefore be any unintended disease or injury or clinical signs (including an abnormal laboratory finding) in subjects, users or other persons whether or not considered related to the investigational medical device. A serious adverse event (SAE) is defined as an AE that: * led to a death, injury or permanent impairment to a body structure or a body function; * led to a serious deterioration in health of the subject, that either resulted in: a life-threatening illness or injury, or a permanent impairment of a body structure or a body function, or in-patient hospitalization or prolongation of existing hospitalization, or in medical or surgical intervention to prevent life threatening illness * led to foetal distress, foetal death or a congenital abnormality or birth defect.
The number of adverse events (AEs) or serious adverse event (SAEs)
Time Frame: Between screening visit and 24 weeks (measured at each visits)
An adverse event (AE) is any untoward medical occurrence in a patient exposed to a medical device and which does not necessarily have a causal relationship with this medical device. An AE can therefore be any unintended disease or injury or clinical signs (including an abnormal laboratory finding) in subjects, users or other persons whether or not considered related to the investigational medical device. A serious adverse event (SAE) is defined as an AE that: * led to a death, injury or permanent impairment to a body structure or a body function; * led to a serious deterioration in health of the subject, that either resulted in: a life-threatening illness or injury, or a permanent impairment of a body structure or a body function, or in-patient hospitalization or prolongation of existing hospitalization, or in medical or surgical intervention to prevent life threatening illness * led to foetal distress, foetal death or a congenital abnormality or birth defect.
The number of patients with neurological changes during the follow-up period according to the evaluation of nerve root pain, sensory deficit and motor deficit
Time Frame: Between screening visit and 24 weeks (measured at each visits)
The neurological evaluation will look more specifically for: * The presence or absence of nerve root pain and its localisation (i.e. Lassegue test) * The presence of deferred pain in the leg without deficit * The presence or absence of sensory deficit and its localisation * The presence or absence of motor deficit and its classification from grade 1 to 5 (0 - Total Paralysis, 1 - Palpable or Visible, 2 - Active Movement, gravity eliminated, 3 - Active Movement, against gravity, Contraction, 4 - Active Movement, against some resistance, 5 - Active Movement, against full resistance (normal muscular force))
The change of the water content of the nucleus measured in milliseconds on the MRI during the follow-up period
Time Frame: Between screening visit and 24 weeks (measured at each visits)
The Magnetic resonance imaging (MRI) will allow the observation.
The modifications observed after the injection in the adjacent tissues of the injected nucleus
Time Frame: Between screening visit and 24 weeks (measured at each visits)
The Magnetic resonance imaging (MRI) will allow the observation of the corresponding adjacent tissues: * Annulus fibrosus * Endplates * Facets
The change of the intervertebral height in millimetres of the injected disc
Time Frame: Between screening visit and 24 weeks (measured at each visits)
The Magnetic resonance imaging (MRI) will allow the observation.
The change of the DXM gel position in relation to posterior and anterior limit of the annulus fibrosus and vertebral disc end-plates
Time Frame: Between screening visit and 24 weeks (measured at each visits)
The Magnetic resonance imaging (MRI) will allow the observation.
Secondary Outcomes
- The change of the intervertebral height in millimetres of the injected disc(Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L))
- The change of the DXM gel position in relation to posterior and anterior limit of the annulus fibrosus and vertebral disc end-plates(Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L))
- Oswestry disability index (ODI)(Measured and compared to baseline at the different time points of the flowchart according to the cohort (over 24 to 48 weeks))
- Visual analogue scale (VAS) self-assessment(Measured and compared to baseline at the different time points of the flowchart according to the cohort (over 24 to 48 weeks))
- Working status(measured and compared to baseline at the different time points of the flowchart according to the cohort (over 24 to 48 weeks))
- The number of patients with at least one adverse event (AE) or serious adverse event (SAE)(Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L))
- The number of adverse events (AEs) or serious adverse event (SAEs)(Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L))
- The number of patients with neurological changes during the follow-up period according to the evaluation of nerve root pain, sensory deficit and motor deficit(Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L))
- The change of the water content of the nucleus measured in milliseconds on the MRI during the follow-up period(Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L))
- The modifications observed after the injection in the adjacent tissues of the injected nucleus(Over 48 weeks for the first cohort (1L) / 36 weeks for the second cohort (2L) / 24 weeks for the third cohort (1-2L))