Intradiscal Platelet Rich Plasma

Phase 4

Terminated

Conditions: Discogenic Pain
Low Back Pain
Chronic Pain

Interventions: Drug: Low back intradiscal injection of platelet rich plasma (PRP)

Registration Number: NCT04544709

Lead Sponsor: University of Utah

Brief Summary: To assess changes in pain and function in patients with discogenic low back pain after a standard of care intradiscal injection of Platelet-Rich Plasma (PRP).

Detailed Description: Low back pain is one of a few conditions which affects all individuals through the lifespan. The etiology of low back pain is multifactorial and in many cases self-limiting, however it also is the leading cause for working age adults to be disabled with more than $87 billion spent on low back pain disorders in 2013 Lumbar disc herniation and internal disc disruption are two causes more common in these younger age groups reaching 39-42% with a predicted probability above 60% until age 50y. While the natural history of disc herniation suggests most individuals will return to a prior level of function in 3-6 months, there is a high rate of recurrent episodes which can cause short-term disability. Continued pain from a discogenic source can lead to decreased activity levels and accelerate degenerative changes in the disc and facet joints as described by Kirkaldy-Willis.

Current guidelines for treatment of axial low back pain from discogenic sources including those with radiculopathy include a 6-12-week course of conservative care including medications, therapy, acupuncture, chiropractic and exercise before an interventional paradigm of injections and/or surgical treatment. For those individuals who do not improve with conservative care and have predominately axial pain, options are limited as success rates from epidural steroid injections and surgery are 50% or less. Other treatments include chymopapain injection, intradiscal electrothermal annuloplasty (IDET), nucleoplasty, methylene blue injection, ozone injection , fibrin sealant injections. All of which have 50% or less likelihood of reducing pain more than 50%, although much of this data is from uncontrolled or prospective case-control studies only.

Platelet- rich plasma (PRP) injections stand apart from those listed above in that they are purported to be "regenerative" interventions for the diseased lumbar disc. PRP is a concentrated injectant of growth factors and anabolic factors which have in vitro and animal studies that have demonstrated upregulated proteoglycan synthesis and nucleus pulposus proliferation, restoration of disc height, healing of annular puncture wounds and anti-inflammatory effect with down regulation of TNF-alpha and IL-1. There has been limited clinical trials in humans on the effect of intradiscal PRP, including 3 trials of which 1 is a RCT and 2 are prospective series. Efficacy of intra-discal injection has shown statistically significant benefits in reduction in pain, improvement in physical function at follow-up points from 3-24 months. Each of these trials have limited sample sizes, short duration follow-up and lack of a standardized PRP preparation, making the generalizability difficult.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

Inclusion Criteria

Age greater than 18 years of age at day of enrollment.
Clinical diagnosis of refractory discogenic low back pain for >3 months.
Magnetic resonance imaging pathology consistent with clinical symptoms/signs or positive lumbar provocative discography according to SIS/IASP standards at one or two levels.
Back pain greater than leg pain with an intensity of at least 4/10 or higher using the Numerical Rating Scale (NRS).
Pain duration of more than 12 weeks despite trial of conservative therapy (medications, physical therapy, or chiropractic care) for 2 months.

Exclusion Criteria

Refusal to participate, provide consent, or provide follow-up information for the 24-month duration of the study.
Contraindications to intradiscal injection of PRP (active infection, bleeding disorders, current anticoagulant or antiplatelet medication use, allergy to iodinated contrast, penicillin or clindamycin and pregnancy or breastfeeding).
More than 2 levels of clinical or discogram proven pain.
Non-discogenic source of low back pain as identified by separate diagnostic blocks.
Negative lumbar provocation discography.
Active moderate to severe lumbar radiculopathy.
Intradural disc herniation.
Spinal fracture within the past 6 months.
Steroid injection in the spine within the last 30 days.
Any intradiscal injection other than contrast dye or anesthetic in the last 30 days.
Prior fusion at level considered to be the source of the pain.
Prior lumbar spine surgery within the last 6 months.
AP diameter of spinal canal less than or equal to 9mm at level to be treated.
Severe uncontrolled medical condition.
Moderate to severe hepatic dysfunction.
Severe psychological illness.
History of Inflammatory arthritis.
Malignancy within past 5 years except basal cell or squamous cell skin cancer.
Current use of equal to greater than 30mg morphine-equivalent per day of opioid use.
A history of alcohol or drug abuse within past 5 years.
Use of any investigational drug within past 30 days.
A known allergy or sensitivity to citrate (used for processing PRP).
Severe anaphylactic/anaphylactoid reaction to any medications used.
Pending litigation involving subject's back pain.
No insurance coverage for any subsequent tests or procedures.
Disc protrusion greater than 5mm from base of vertebral body.
Greater than 50% disc height loss at involved level(s).
Inability or unwillingness to continue rehabilitation protocols.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Discogenic Low Back Pain	Low back intradiscal injection of platelet rich plasma (PRP)	Patient with Refractory Discogenic Low back pain who will be scheduled for platelet rich plasma injection as standard of care.

Primary Outcome Measures

Name	Time	Method
Numeric Rating Scale for Low Back Pain at 2-Month Follow-up	2 months	Proportion of participants with ≥80% and ≥50% reductions from baseline in 7-day average low back pain intensity scores on the Numeric Rating Scale (NRS) at the 2-month follow-up assessment.

Secondary Outcome Measures

Name	Time	Method
PROMIS PF CAT Change Scores	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months	Patient-Reported Outcomes Measurement Information System Physical Function Computerized Adaptive Testing (PROMIS PF CAT) measures limitations of physical activity on a scale of 0 to 100, with higher scores indicating fewer limitations. PROMIS PF CAT change scores were calculated by subtracting baseline scores from follow-up scores, so that positive change scores represent improvements to functional limitations.
Patient Global Impression of Change (PGIC) Scores	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months	Patient Global Impression of Change (PGIC) scores represent participants' overall satisfaction after an intervention. Participants are asked to rate their perception of change on a scale of 1 to 7, where 1="very much worse", 2="much worse", 3="worse", 4="no change", 5="improved", 6="much improved", and 7="very much improved".
Oswestry Disability Index (ODI) Change Scores	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months	The Oswestry Disability Index (ODI) is an instrument used in clinical and research applications to quantify disability due to low back pain as a percentage score (0-100%) based on patients' self-reported level of function in activities of daily living, with higher scores indicating greater disability. ODI change scores were calculated by subtracting baseline scores from follow-up scores, so that negative change scores correspond to functional improvements.
Median Change in Low Back Pain Numeric Rating Scale (NRS) Score	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months	The Numeric Rating Scale (NRS) was used to quantify low back pain by asking patients to rate their pain intensity on an 11-point scale ranging from 0 to 10, with 0 representing "no pain at all" and 10 representing "the worst pain imaginable". NRS change scores were calculated by subtracting baseline scores from follow-up scores, so that negative change scores correspond to decreases in low back pain.
Proportion of Patients With ≥30% Improvement From Baseline on the Oswestry Disability Index (ODI)	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months	The Oswestry Disability Index (ODI) is an instrument used in clinical and research applications to quantify disability due to low back pain as a percentage score based on patients' self-reported level of function in activities of daily living.
Proportion of Patients With a ≥6 Score on Patient Global Impression of Change (PGIC)	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months	Patient Global Impression of Change is a scale which measures participant reported satisfaction after an intervention. The outcome was measured as the percent of patients reporting a PGIC score of 6-7 (indicating "much improved" and "very much improved").
Proportion of Patients With a Medication Quantification Scale (MQS) III Score Reduction From Baseline of ≥6.8 Points	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months	A score of 6.8 points on the MQS III is equivalent to approximately 10 daily morphine equivalents
Pain and Sleep Questionnaire 3-Item Index (PSQ-3) Change Scores	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months	The 3-Item Pain and Sleep Questionnaire is an instrument used in clinical and research applications to measure the impact of pain on sleep in chronic pain populations. A higher total score (range 0 to 300) indicates a greater extent of pain-related sleep interference. PSQ-3 change scores were calculated by subtracting baseline scores from follow-up scores, so that negative change scores correspond to reductions in pain-related sleep interference.
Patient Satisfaction Scores	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months	The Patient Satisfaction Score represents patient satisfaction with the healthcare received using a five-point Likert scale where 1 = "very dissatisfied"; 2 = "dissatisfied"; 3 = "neither satisfied nor dissatisfied"; 4 = "satisfied"; and 5 = "very satisfied".
Opioid Consumption in Daily Morphine Equivalents	1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months
Proportion of Patients Who Underwent Lumbar Spinal Surgery During the Study Period	24 months, 36 months