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Trial registered on ANZCTR


Registration number
ACTRN12619000307101
Ethics application status
Approved
Date submitted
16/02/2019
Date registered
28/02/2019
Date last updated
3/03/2023
Date data sharing statement initially provided
28/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the safety and efficacy of IDSD (an injectable medical device) when treating low back (lumbar) pain due to Degenerative Disc Disease (DDD) in symptomatic adults.
Scientific title
Genipin Microinvasive Device for Treatment of Low Back Pain from Degenerative Disc Disease- CE Marking Safety and Efficacy Study
Secondary ID [1] 297429 0
Nil known
Universal Trial Number (UTN)
Trial acronym
GEM-SE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Low Back Pain 311602 0
Condition category
Condition code
Musculoskeletal 310230 310230 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention Type- Device,
Intervention Name - IDSD,
Intervention Description - IDSD is an injectable medical device intended to treat intervertebral disc degeneration and associated low back pain by providing localized tissue reinforcement and mechanical stabilization. The IDSD medical device is injected directly into the disc annulus fibrosus tissue. IDSD contains a plant derived protein cross-linker (Genipin) that is injected as a buffered liquid combined with a contrast agent by a clinician experienced with image-guided injections to the spinal disc. The choice of contrast agent is left to the investigator. 180-370 mg/ml Isovue, Omnipaque, Iopamiro, and Ultravist have been previously tested. The clinician is provided with an injection training document, a virtual training session, detailed instructions for use, and optional cadaveric injection training. IDSD is a single-use device comprising two 5 mL glass vials containing the sterile cross-linker and buffered solution. The components are combined with a contrast agent just prior to the fluoroscopic image-guided interventional procedure. The genipin forms polymers as it diffuses through the tissue and adds these polymers to the native collagen matrix in the disc, forming covalent bonds between the ends of the genipin polymers and the native disc collagen. The increased mechanical support to the tissue and intervertebral joint are intended to reduce or eliminate corresponding low back pain.
All study participants will undergo implantation of IDSD at 1 or 2 symptomatic spinal levels during a single intervention session. The volume of IDSD implanted is determined by the cross-sectional size of the target disc(s).
The procedure takes approximately 45 minutes or less.
Intervention code [1] 313681 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319112 0
Serious Adverse Events at 1 month.

Serious adverse events will be assessed by the site principal investigator and may include significant increase in low-back pain (NRS increase of 2 points or VAS increase of >20mm) over baseline level lasting more than 14 days, Indications of chronic inflammatory response, lasting more than 21 days and unresponsive to anti-inflammatory or neuropathic pain medicines, Any neuromuscular deterioration or other adverse response to treatment requiring subsequent treatment (excluding anti-inflammatory or neuropathic pain medication) and/or hospital stay, Any injection related serious adverse event including dural tear, hematoma with neurological involvement, nerve root involvement that persists more than 21 days and is unresponsive to anti-inflammatory or neuropathic or non-opioid pain medications, injection site irritation with drainage or infection and Intractable pain, urinary tract infection lasting more than 14 days, systemic infection, thromboembolic event, etc.
Timepoint [1] 319112 0
1-month post procedure (primary) assessed at 1-2 weeks, at 3 months, at 6 months, and at 12 months, post implantation.
Primary outcome [2] 319113 0
Change in pain assessed via numerical pain rating scale at 3 months compared with baseline using a Visual Analog Scale for low-back pain
Timepoint [2] 319113 0
3-months post-implantation.
Primary outcome [3] 319196 0
Change in disability assessed via Oswestry Disability Index rating at 3 months compared with baseline
Timepoint [3] 319196 0
3 months
Secondary outcome [1] 367008 0
Change in pain assessed via numerical pain rating scale at 1-2 weeks, 1 month, 6 and 12 months compared with baseline using a Visual Analog Scale for low-back pain
Timepoint [1] 367008 0
1-2 weeks, 1 month, 6 and 12 months
Secondary outcome [2] 367009 0
Change in disability assessed via Oswestry Disability Index rating at 1-2 weeks, 1, 6 and 12 months compared with baseline
Timepoint [2] 367009 0
1-2 weeks, 1 month, 6 and 12 months
Secondary outcome [3] 367246 0
Change in flexion-extension instability assessed via radiographic imaging and the QSI metric (Quantitative Stability Index, quantifies the number of standard deviations above the mean (of an asymptomatic, radiographically normal population) for a measured amount of translation per degree of rotation (TPDR)) at 1 and 3 months compared to baseline
Timepoint [3] 367246 0
1 month, 3 month

Eligibility
Key inclusion criteria
1. Adults 18-60 years old
2. Degenerative Disc Disease at 1 or 2 levels between L2 and S1, with clinical presentation of discogenic pain where the central back pain is greater than radicular pain (leg, hips, or buttocks), confirmed by:
a. MRI correlative to the affected segment, and/or
b. discography with concordant pain within 6 months- If imaging and examination can
not conclusively determine which disc is the source of the pain, a discogram is
mandated for confirmation.
3. Failed non-operative treatment which may include injections or radiofrequency
denervation of medial lumbar and lateral sacral branches (failed response is considered
when pain relief lasted less than or equal to 3 months)
4. Preoperative Numeric Rating Scale (NRS) score for back pain greater than or equal to 4 or Visual Analog Score for back pain greater than or equal to 40 mm.
5. Preoperative Oswestry Disability Index (ODI) score greater than or equal to 30%
6. Documented symptoms for a cumulative minimum of 3 months
7. Participant is competent to sign the informed consent
8. Participant voluntarily signs the participant informed consent form and agrees to the
release of medical information for purposes of this study
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Symptomatic DDD at more than 2 levels
2. Less than 3 months of back pain
3. Previous diagnosed Paget's disease, osteomalacia, other metabolic bone disease or insulin-dependent diabetes
4. Evidence of spinal osteopenia or osteoporosis (radiographic or DEXA)
5. Active systemic or spine infection
6. Previous device or therapeutic interventions on the target disc (excluding those listed in the Inclusion Criteria)
7. Any surgery at the index level and any extensive surgery (fusion, laminectomy, artificial disc) at any level
8. Chronic steroid use (except for inhaled steroids)
9. Other diagnosed causes of back pain or neuropathy such as vertebral fracture, facet joint or vertebral arch (spondylolysis) generated pain, rheumatoid arthritis, cauda equine syndrome, spinal fracture within last 6 months, and sacroiliac joint pain
10. Previous treatment of target disc level with steroid injection in past 3 months
11. Active malignancy
12. Spinal tumor
13. Immune compromised participants
14. Lumbar scoliosis > 15 degrees
15. Evidence of disc herniation or large penetrating fissure including current diagnosis of sciatica, disc bulge > 5mm with radicular pain, or abnormal neurological examination (excluding diminished pin prick test), or in the case of previous sciatica (not current) presence of penetrating disc tear confirmed by observation of Dallas 5 disc tear (Dallas Discogram Classification System) during (mandatory) pressure-controlled discography using an automated injection device.
16. Symptomatic spinal stenosis
17. Congenital or degenerative spondylolisthesis (grade 2 and 3)
18. Psychological comorbidities that could contribute to the need for seeking medical treatment (e.g., depression, anxiety,cPTSD, borderline PD, schizophrenia, substance abuse)
19. Anticipated compliance problems (e.g., transportation, dementia, computercilliteracy)
20. Currently participating in another investigational study that could interfere with the outcome measurements of this study
21. Known anaphylactic reaction to contrast dye
22. Opioid daily intake > 90 MEQ
23. Not able to communicate with study center staff sufficiently to complete study questionnaires
24. Positive urine pregnancy test
25. History of unexplained, easy or persistent bruising or bleeding, bleeding from the gums, or bleeding problems experienced in previous surgical procedures
26. Congenital or acquired coagulopathy or thrombocytopenia; or currently taking anticoagulant, antineoplastic, antiplatelet, or thrombocytopenia-inducing medications, or undergoing radiation therapy
27. Annular rim tear suspected by posterolateral located high intensity zone or a focal disc protrusion on MRI, confirmed by observation of Dallas 5 disc tear (Dallas Discogram Classification System) during (mandatory) pressure-controlled discography using an automated injection device.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This study will enroll up to 50 participants. Based on the primary safety hypothesis that device related Serious Adverse Events at 1-month post-treatment will be less than 25%, Simon’s and Jung’s two-stage principles have been used to determine the first stage size, study stoppage criteria (4 or more device related serious adverse events in the first 16 participants), second stage size, and final assessment of treatment safety-- the null hypothesis will be rejected if 8 or more SAEs are observed in 49 patients (actual 16%). This design yields a type I error rate of 0.05 and power of 0.85 when the true rate of device related serious adverse events at 1-month post-procedure is 10% or less. Baseline clinical and participant features will be summarized using standard descriptive statistics including means, medians, standard deviations, ranges for continuous measures and frequencies and percentages for categorical measures. Adverse event data will be summarized as the frequency of events and the percentage of participants experiencing the event. Changes from baseline in the efficacy endpoints including pain and disability scales, instability, lumber range of motion, lordosis, medication use and quality of life, will be statistically evaluated using paired t-tests and Wilcoxon signed rank tests as appropriate. These differences will be summarized as means with 95% confidence intervals or medians and interquartile ranges (IQRs) as appropriate. A two-tailed p-value <0.05 will be used to determine statistical significance.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/03/2019
Actual
4/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
15
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC

Funding & Sponsors
Funding source category [1] 301999 0
Commercial sector/Industry
Name [1] 301999 0
Intralink-Spine Australia Pty. Ltd.
Country [1] 301999 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Intralink-Spine Australia Pty. Ltd.
Address
58 Gipps Street, Collingwood, VIC 3066
Country
Australia
Secondary sponsor category [1] 301779 0
Commercial sector/Industry
Name [1] 301779 0
Avania
Address [1] 301779 0
13/76 Reserve Road, Artarmon, NSW 2064
Country [1] 301779 0
Australia
Other collaborator category [1] 280559 0
Commercial sector/Industry
Name [1] 280559 0
Intralink-Spine, Inc.
Address [1] 280559 0
1501 Bull Lea Road, Suite 103 Lexington, KY 40511
Country [1] 280559 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302674 0
Bellberry Human Research Ethics Committee H
Ethics committee address [1] 302674 0
129 Glen Osmond Rd,
Eastwood, Adelaide, SA 5063
Ethics committee country [1] 302674 0
Australia
Date submitted for ethics approval [1] 302674 0
Approval date [1] 302674 0
10/01/2019
Ethics approval number [1] 302674 0

Summary
Brief summary
The purpose of this study is to evaluate the safety and clinical effectiveness of the Réjuve medical device when treating low back pain due to Degenerative Disc Disease in adults. Degenerative disc disease in the lower back refers to a syndrome in which a compromised or damaged disc causes low back pain with or without pain radiating to the leg. Réjuve is an injectable soluble material that is considered as a medical device. Réjuve chemically bonds with the collagen in the spinal disc tissue to structurally strengthen the degraded disc and stabilize the spinal joint. These tissue strengthening and joint stabilizing effects, if they occur to the extent intended, may reduce the amount of back pain that the study participant experiences. Réjuve contains a substance called Genipin that causes chemical bonding in load supporting tissues. These chemical bonds are similar to, and are intended to mimic, naturally-occurring chemical bonds in the tissue that typically accumulate in spinal discs over many years. Genipin is made from purified plant sources (Gardenia fruit) and is dissolved in a special buffer liquid prior to being injected into the spinal disc using image-guided injection techniques. A special dye called a contrast agent that is not part of Réjuve is also added to Réjuve before it is injected so that what is being injected can be seen by the physician doing the injection.
There are two primary hypotheses being tested in this study. The first hypothesis involves the safety of the device and its image-guided delivery to the study participant. It is hypothesized that Réjuve can be safely applied to degenerated intervertebral discs as evidenced by a clinically acceptable prevalence of Serious Adverse Events reported at 1 month post-procedure. The second primary hypothesis involves the clinical effectiveness of the device. It is hypothesized that the clinical success rate at 3 months after the Réjuve implantation procedure will be greater than or equal to 50%. Clinical success is defined as successful injection delivery of Réjuve to the targeted disc without the occurrence of serious adverse events with a significant reduction of pain and disability using standard assessment metrics. Objective imaging data will also be used to validate reduction of pain post-treatment. A maximum of 50 participants will be enrolled in this clinical study at 2-5 clinical centers. Safety and clinical effectiveness assessments will be carried out through 12 months post-implantation procedure.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91022 0
Dr Geoffrey Rosenberg
Address 91022 0
Hurstville Private Hospital,
37 Gloucester Road, Hurstville NSW 2220
Country 91022 0
Australia
Phone 91022 0
+61 295886399
Fax 91022 0
Email 91022 0
[email protected]
Contact person for public queries
Name 91023 0
Tom Hedman
Address 91023 0
Intralink-Spine, Inc.
1501 Bull Lea Rd. Suite 103 Lexington, KY 40511
Country 91023 0
United States of America
Phone 91023 0
+1 512 8188468
Fax 91023 0
Email 91023 0
[email protected]
Contact person for scientific queries
Name 91024 0
Tom Hedman
Address 91024 0
Intralink-Spine, Inc.
1501 Bull Lea Rd. Suite 103 Lexington, KY 40511
Country 91024 0
United States of America
Phone 91024 0
+1 512 8188468
Fax 91024 0
Email 91024 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEarly Clinical Results of Intervertebral Joint Stabilization by Injectable Load-Sharing Polymers.2023https://dx.doi.org/10.2147/JPR.S413104
N.B. These documents automatically identified may not have been verified by the study sponsor.