Safety and Efficacy of PRP for Treatment of Disc Pain

Study Overview
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Brief Summary
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This is a multi-center, randomized, controlled, double-blind clinical trial comparing hemocyte autograft (platelet rich plasma) to control injection (placebo) in subjects with reported cervical, thoracic or lumbar pain for at least 3 months with Pfirrmann grade changes at 7 or less and who are being considered for discography in order to identify pain generator discs in evaluation of potential surgical candidates.

Detailed Description
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The study will recruit 180 subjects: 60 suffering from lumbar discogenic pain, 60 suffering from thoracic discogenic pain and 60 suffering from cervical discogenic pain. In each arm 40 study subjects will be randomized to receive hemocyte autograft, while 20 will be randomized to receive contrast as the control group. All subjects will have blood drawn (50 cc) from any access site and have it prepared for hemocyte autograft. Using a 20 gauge introducer and 25 gauge disc needle, subjects randomized to active condition will have exactly 3 cc of hemocyte autograft placed in a 3 cc syringe while subjects randomized to placebo will have exactly 3 cc of saline placed in a 3 cc syringe. The syringe barrels and tubing will be completely covered with opaque tape so that the injector is blinded to the contents. For both conditions, 1-2 cc of designated injectant (PRP for active, saline for placebo) will be injected into the nucleus pulposus of each identified treatment level disc for lumbar; 0.5-1 cc for thoracic and 0.5-1 cc for cervical. Primary endpoint will be at 8 weeks after injection. After 8 weeks subjects who received placebo are eligible for crossover to treatment arm with hemocyte autograft, and subject who received treatment arm are eligible for surgery if not improved.

Official Title
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A Multi-Center, Randomized, Controlled, Double-blind Study Evaluating Safety and Efficacy of Hemocyte Autograft for Treatment of Single-Level and Multi- Level Lumbar, Thoracic and Cervical Discogenic Pain

Conditions
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Discogenic Pain

Intervention / Treatment
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* Device: High yield pure PRP
* Other: Placebo
* Device: ProPlaz PPC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female at least 18 years of age. Clinically suspected discogenic pain in the cervical, thoracic or lumbar spine. Bring considered for discography in order to identify source of pain in the evaluation of potential surgical candidates. History of neck pain or mid or low back pain for at least 3 months. Failed to respond to conservative therapies that include physical therapy and analgesics. Documented Pfirrmann grade changes of 7 or less at each treatment level as represented by an MRI no more than 12 months old (extravasation not excluded). Exclusion Criteria: Unresolved neck or back pain from a previous cervical, thoracic or lumbar surgery at any level. Any contraindication for discography or surgery Significant signs or symptoms of root or cord compression at treatment levels. Any diagnosis of a concurrent pain disorder or other concurrent cause of disability. Daily opioid requirements of greater than180 mg oral morphine equivalent (OME) per day. Current active systemic infection, or history of disc infection. Untreated disabling thought or mood disorder. Inability to provide informed consent including subjects in a socially compromised condition such as prisoners.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a multi-center, randomized, controlled, double-blind clinical trial comparing hemocyte autograft (platelet rich plasma) to control injection (placebo) in subjects with reported cervical, thoracic or lumbar pain for at least 3 months with Pfirrmann grade changes at 7 or less and who are being considered for discography in order to identify pain generator discs in evaluation of potential surgical candidates. Randomization ratio was 2:1. After 8 weeks subjects who received placebo are eligible for crossover to treatment arm with hemocyte autograft, and subject who received treatment arm are eligible for surgery if not improved. For subjects who cross over, follow-up schedule will reset with visits at 8 weeks and 26 weeks post-crossover.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRP/Hemocyte Autograft Intervention Arm<br>All subjects will have blood drawn (50 cc) from any access site and have it prepared for hemocyte autograft. Using a 20 gauge introducer and 25 gauge disc needle, subjects randomized to active condition will have exactly 3 cc of hemocyte autograft placed in a 3 cc syringe. The syringe barrels and tubing were covered with opaque tape so that the injector was blinded to the contents. 1-2 cc of PRP was injected into the nucleus pulposus of each identified treatment level disc for lumbar; 0.5-1 cc for thoracic and 0.5-1 cc for cervical. | Device: High yield pure PRP<br>* The investigational product is hemocyte autograft derived from the subject's own blood. Subjects with a clinical diagnosis of discogenic pain had a discogram with ¼ cc to ½ cc of contrast injected by hand (leaving up to ½ cc contrast in the needle lumen and connecting tube); any concordant pain will be noted. Subjects received the injectant delineated by coordinator-provided randomization. Subjects were awake for the entirety of study treatment procedure. All subjects had blood drawn (50 cc) from any access site and double-centrifuged using the EmCyte Hemocyte Autograft system; the first spin separated the buffy coat, the second spin and subsequent siphoning separated a purified platelet sample.<br>* Other names: PRP;Device: ProPlaz PPC<br>* Trademarked name of an FDA-cleared product<br>* Other names: BioRich Medical ProPlaz Protein Plasma Concentrator;|
| Placebo Comparator: Placebo Control Arm<br>All subjects will have blood drawn (50 cc) from any access site and have it prepared for hemocyte autograft. Using a 20 gauge introducer and 25 gauge disc needle, subjects randomized to placebo condition will have exactly 3 cc of saline placed in a 3 cc syringe. 1-2 cc of saline was injected into the nucleus pulposus of each identified treatment level disc for lumbar; 0.5-1 cc for thoracic and 0.5-1 cc for cervical. | Other: Placebo<br>* Placebo injections will have saline placed in centrifuges and run for the duration required for PRP preparation. 3cc of saline will be placed in 3 cc syringes with opaque tape around the barrel to cover the fluid chamber. 1-2 cc of saline will be injected into the nucleus pulposus of each treatment level disc under fluoroscopy for lumbar; 0.5-1 cc for thoracic and 0.5-1 cc for cervical.<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Specific Functional Scale (PSFS) | The primary objective of this study is to determine safety and efficacy of a single injection of hemocyte autograft into diseased discs for the treatment of back and neck pain. The PSFS is a self-report, patient-specific outcome measure designed to assess functional change in patients with pain and musculoskeletal disorders. The total score = the sum of the activity scores (10 maximum, which reflects a better level of functioning)/the number of activities (7 maximum). At least two points improvement on the average Pain Specific Functional Scale (PSFS). | 8 weeks from baseline | 
| Adverse Event Reporting | Adverse events (AEs) and any other untoward signs or symptoms were collected at each study timepoint starting at the treatment injection. Serious adverse events (SAEs) determined by the investigator to be related to the study treatment were formally recorded. [NOTE: NONE REPORTED THROUGHOUT STUDY DURATION] | Baseline to 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Pain Rating Scale (NRPS) | The NRPS is a unidimensional measure of pain intensity for adults. The 11-point numeric scale ranges from '0' representing 'no pain' to 10 representing 'worst possible pain.' The NPRS can be administered verbally or graphically for self-completion. The respondent is asked to indicate the numeric scale value that best describes the intensity of their pain within the last 24-hours. Clinical improvement was denoted by at least 3 points improvement in Numeric Pain Rating Scale (NPRS) | 8 weeks from baseline | 
| Oswestry Disability Index (ODI) | A measure to gauge improvement in pain symptoms among lumbar and thoracic spine conditions. The ODI is a patient-based questionnaire which gives a subjective percentage score of functionality/disability for a list of activities of daily living among those rehabilitating from lower back pain. There are 6 statements scored from 0-5 (0 is the least pain/no pain, 5 is the greatest level of pain). Clinical improvement is characterized by more than 10% improvement in the ODI from baseline (calculated by [total scored/total possible score]*100). | 8 weeks from baseline | 
| Neck Disability Index (NDI) | The most commonly-used self-report measure to gauge improvement in pain symptoms among cervical spine conditions. The NDI is comprised of 10 items (each scored on a 0-5 rating scale, in which zero reflects no pain and five means worst pain imaginable) including pain, personal care, reading, lifting, headaches, concentration, work ,driving, sleeping, and recreation. A higher score indicates greater level of disability. The NDI can be scored as a raw score of doubled and expressed as a percentile. 0-4 points (0-8%) = no disability. 5-14 points (10-28%) = mild disability. 15-24 points (30-48%) = moderate disability. 25-34 points (50-64%) = severe disability. 35-50 point (70-100%) = complete disability. Clinical improvement was indicated by improvement of at least 10% from baseline. | 8 weeks from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lumbar Spine, Thoracic Spine, Cervical Spine