Internal Disc DisruptionNCT04102761

The Use of PRP and BMC in Patients With Internal Disc Disruption Multicenter Prospective Randomized Controlled Trial in Patients With Internal Disc Disruption

A study testing Intradiscal PRP & BMC Injections in people with Internal Disc Disruption, run by Annu Navani at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The condition being studied is chronic low back or leg pain in patients with internal disc disruption (IDD). The intervention to be studied is the intradiscal delivery of autologous Platelet Rich Plasma (PRP) or bone marrow concentrate (BMC) into the nucleus pulposus of the disrupted disc(s). Read more about this study

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Internal Disc Disruption
What is being tested?: Intradiscal PRP & BMC Injections
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 45 participants
Where: 4 sitesUnited States
Study dates: 27 Mar 2018to 31 Dec 2020
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

A high index of suspicion for discogenic pain, i.e. painful degenerative discs with or without contained protrusions
Age greater than 18 and less than 70 years
Maintained intervertebral disc heights of at least 50%
Pain not generated from facet joints, sacro-iliac joints or any pathology other than discogenic origin.
Pain is not responsive to conservative treatment measures (oral medications, epidural steroid injections, physical therapy)
Pain persists for an extended period of time (i.e., at least 3 months)

Show all 9Show fewer

High intensity zone (HIZ) in annular fissure detected on T2 or STIR MRI, degenerated discs or contained disc protrusions.
No evidence of contraindications to undergo procedure such as pregnancy, active infection, bleeding disorder, or metastatic cancer
English speaking

Who cannot join

Disc extrusions, disc sequestrations, severe spinal stenosis, or severe disc degeneration with grade 5 Pfirmann index or with Modic 3 level change.
Patient refusal
Presence of a known bleeding disorder
Pregnancy
Systemic or local infection
Presence of an unstable medical or psychiatric condition

Show all 10Show fewer

Prior intradiscal procedure (ie. IDET, Nucleoplasty)
Inaccessibility to discs such as fusion
Non-English speaking
Prior fusion surgery

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Alex Hames
Campbell, California, 95008
The Orthohealing Center
Los Angeles, California, 90025
Nexus Pain Care
Provo, Utah, 84604
Texas Spine and Joint Hospital
Tyler, Texas, 75701

Other trials in United States

About this study

Official title: Platelet Rich Plasma and Bone Marrow Aspirate for Lumbar Intradiscal Injections: A Multicenter Prospective Randomized Controlled Trial in Patients With Internal Disc Disruption

Read the detailed description

This multi-center randomized controlled pilot trial will be the first to evaluate the response of PRP and BMC for discogenic pain by direct comparison. The investigators propose to incorporate a crossover design that compares placebo to two treatment modalities (i.e. Neutrophil-Poor PRP [NP-PRP] and BMC).

If the investigators can demonstrate statistically significant and clinically meaningful improvements in study's primary and secondary outcome measures, this study will have identified a natural, effective and sustainable treatment for discogenic back pain that currently accounts for the highest level of disability in US. This will help guide physicians in the choice of care between surgical and conservative treatment options when treating patients.

Conditions: Internal Disc Disruption
Being tested: Intradiscal PRP & BMC Injections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Intradiscal PRP & BMC InjectionsProcedure or surgery
The intervention to be studied is the intradiscal delivery of autologous Platelet Rich Plasma (PRP) or bone marrow concentrate (BMC) into the nucleus pulposus of the disrupted disc(s).

Study groups in NCT04102761
Study group	Role	What they receive
Trigger Point Needling	Placebo comparator	The first group will receive a deep trigger point injection of saline into deep tissue. Receives: Procedure: Intradiscal PRP & BMC Injections
Platelet Rich Plasma Injection	Active comparator	The Platelet Rich Plasma group will receive an injection of approximately 1-2 mL of Platelet Rich Plasma into the painful disc/discs. Receives: Procedure: Intradiscal PRP & BMC Injections
Bone Marrow Aspirate Injection	Active comparator	The third group will receive an injection of approximately 1-2 mL of Bone Marrow Concentrate into the painful disc/discs. Receives: Procedure: Intradiscal PRP & BMC Injections

What is being measured

The primary outcome is the main question the study is designed to answer.

Worsening of Disc Pathology with Injection of Biologics
Pre and post op discs will be examined and compared for worsening pathology.
Measured: 24 weeks post procedure
Improvement in Disc Pain with Injection of Biologics
Pre and post op Pain will be measured and compared by Numeric Rating Scale (NRS) Numeric Pain Rating Scale (NRS): Measured from 0-10, 0 minimum score (better outcome) and 10 maximum score (worse outcome) Oswestry Low back disability (ODS): Measured from 0-50, 0 minimum score and 10 maximum score. The numbers are then calculated into percentages between 0% (minimum disability- better outcome)-100% (maximum disability- worse outcome) NASS Patient satisfaction Index (NASS): Measured from 0-4, 0 (better outcome) and 4 (worse outcome)
Measured: 24 weeks post procedure
Improvement in Function in Patients with Injection of Biologics
Pre and post op function will be measured and compared by Oswestry Disability Index (ODI)
Measured: 24 weeks post procedure

Secondary outcomes (4)

Patient Satisfaction
Patient satisfaction will be measured by the modified North American Spine Surgery (NASS) Outcome Questionnaire
Measured: Pre injection, 1 month post op, 3 months post op, 6 months post op, 1 year.
Hospitalization
Hospitalization will be measured by patient's self report.
Measured: Pre injection, 1 month post op, 3 months post op, 6 months post op, 1 year.
Spine Surgery
Spine Surgery will be measured by patient's self report.
Measured: Pre injection, 1 month post op, 3 months post op, 6 months post op, 1 year.
Medications
Medications will be measured by patient's self report.
Measured: Pre injection, 1 month post op, 3 months post op, 6 months post op, 1 year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Mar 201831 Dec 2020

First posted25 Sep 2019
Study start27 Mar 2018
Primary completion31 Dec 2020
Study completion31 Dec 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (20)Papers the sponsor has linked to this study.
Other trials for Internal Disc DisruptionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Subjects will be assigned to one of three arms of the study. The first group will receive a trigger point injection of saline into the deep tissue. The second group will receive an injection of approximately 1-2 mL of Platelet RP into the painful disc/discs. The third group will receive an injection of approximately 1-2 mL of Bone Marrow Concentrate into the painful disc/discs. No more than three discs will be injected.
Masking: Single blind
Who is masked: Participant
Enrolment: 45 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04102761
Sponsor's protocol ID: N003R113
Status last verified: Aug 2021
First submitted: 17 Apr 2018
Last updated: 9 Aug 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Mehra M, Hill K, Nicholl D, Schadrack J. The burden of chronic low back pain with and without a neuropathic component: a healthcare resource use and cost analysis. J Med Econ. 2012;15(2):245-52. doi: 10.3111/13696998.2011.642090. Epub 2011 Dec 5.
PubMed 22136441
Zhang YG, Guo TM, Guo X, Wu SX. Clinical diagnosis for discogenic low back pain. Int J Biol Sci. 2009 Oct 13;5(7):647-58. doi: 10.7150/ijbs.5.647.
PubMed 19847321
Omlor GW, Nerlich AG, Tirlapur UK, Urban JP, Guehring T. Loss of notochordal cell phenotype in 3D-cell cultures: implications for disc physiology and disc repair. Arch Orthop Trauma Surg. 2014 Dec;134(12):1673-81. doi: 10.1007/s00402-014-2097-2. Epub 2014 Oct 28.
PubMed 25348151
Konttinen YT, Kemppinen P, Li TF, Waris E, Pihlajamaki H, Sorsa T, Takagi M, Santavirta S, Schultz GS, Humphreys-Beher MG. Transforming and epidermal growth factors in degenerated intervertebral discs. J Bone Joint Surg Br. 1999 Nov;81(6):1058-63. doi: 10.1302/0301-620x.81b6.9321.
PubMed 10615986
Wang SZ, Chang Q, Lu J, Wang C. Growth factors and platelet-rich plasma: promising biological strategies for early intervertebral disc degeneration. Int Orthop. 2015 May;39(5):927-34. doi: 10.1007/s00264-014-2664-8. Epub 2015 Feb 5.
PubMed 25653173
Tolonen J, Gronblad M, Vanharanta H, Virri J, Guyer RD, Rytomaa T, Karaharju EO. Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor. Eur Spine J. 2006 May;15(5):588-96. doi: 10.1007/s00586-005-0930-6. Epub 2005 Jun 25.
PubMed 15980999
Fujita N, Imai J, Suzuki T, Yamada M, Ninomiya K, Miyamoto K, Iwasaki R, Morioka H, Matsumoto M, Chiba K, Watanabe S, Suda T, Toyama Y, Miyamoto T. Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc. Biochem Biophys Res Commun. 2008 Jul 25;372(2):367-72. doi: 10.1016/j.bbrc.2008.05.044. Epub 2008 May 19.
PubMed 18492486
Civinini R, Macera A, Nistri L, Redl B, Innocenti M. The use of autologous blood-derived growth factors in bone regeneration. Clin Cases Miner Bone Metab. 2011 Jan;8(1):25-31.
PubMed 22461800
Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 2004 Jan;91(1):4-15. doi: 10.1160/TH03-07-0440.
PubMed 14691563
Hoogendoorn RJ, Lu ZF, Kroeze RJ, Bank RA, Wuisman PI, Helder MN. Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J Cell Mol Med. 2008 Dec;12(6A):2205-16. doi: 10.1111/j.1582-4934.2008.00291.x. Epub 2008 Feb 24.
PubMed 18298653
Masuda K, Oegema TR Jr, An HS. Growth factors and treatment of intervertebral disc degeneration. Spine (Phila Pa 1976). 2004 Dec 1;29(23):2757-69. doi: 10.1097/01.brs.0000146048.14946.af.
PubMed 15564925
Pirvu TN, Schroeder JE, Peroglio M, Verrier S, Kaplan L, Richards RG, Alini M, Grad S. Platelet-rich plasma induces annulus fibrosus cell proliferation and matrix production. Eur Spine J. 2014 Apr;23(4):745-53. doi: 10.1007/s00586-014-3198-x. Epub 2014 Jan 28.
PubMed 24469887
Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, Harrison JR, Gribbin CK, LaSalle EE, Nguyen JT, Solomon JL, Lutz GE. Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study. PM R. 2016 Jan;8(1):1-10; quiz 10. doi: 10.1016/j.pmrj.2015.08.010. Epub 2015 Aug 24.
PubMed 26314234
Pettine KA, Murphy MB, Suzuki RK, Sand TT. Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells. 2015 Jan;33(1):146-56. doi: 10.1002/stem.1845.
PubMed 25187512
Pauza KJ, Howell S, Dreyfuss P, Peloza JH, Dawson K, Bogduk N. A randomized, placebo-controlled trial of intradiscal electrothermal therapy for the treatment of discogenic low back pain. Spine J. 2004 Jan-Feb;4(1):27-35. doi: 10.1016/j.spinee.2003.07.001.
PubMed 14749191

Study at a glance

From the registry record, last updated by the sponsor on 9 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Platelet Rich Plasma and Bone Marrow Aspirate for Lumbar Intradiscal Injections: A Multicenter Prospective Randomized Controlled Trial in Patients With Internal Disc Disruption
ClinicalTrials.gov ID: NCT04102761
Acronym / sponsor ID: N003R113
Conditions: Internal Disc Disruption
Study type: Interventional
Recruitment status: Completed
Enrolment: 45 participants (actual)
Lead sponsor: Annu NavaniUniversity, hospital or other
Collaborators: Andrews Research & Education Foundation
Study start: 27 Mar 2018 (actual)
Primary completion: 31 Dec 2020 (actual)
Study completion: 31 Dec 2020 (actual)
First posted: 25 Sep 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind (participant)
Number of arms: 3
Model description: Subjects will be assigned to one of three arms of the study. The first group will receive a trigger point injection of saline into the deep tissue. The second group will receive an injection of approximately 1-2 mL of Platelet RP into the painful disc/discs. The third group will receive an injection of approximately 1-2 mL of Bone Marrow Concentrate into the painful disc/discs. No more than three discs will be injected.

Arm	Type	Receives
Trigger Point Needling	Placebo comparator	Procedure: Intradiscal PRP & BMC InjectionsThe first group will receive a deep trigger point injection of saline into deep tissue.
Platelet Rich Plasma Injection	Active comparator	Procedure: Intradiscal PRP & BMC InjectionsThe Platelet Rich Plasma group will receive an injection of approximately 1-2 mL of Platelet Rich Plasma into the painful disc/discs.
Bone Marrow Aspirate Injection	Active comparator	Procedure: Intradiscal PRP & BMC InjectionsThe third group will receive an injection of approximately 1-2 mL of Bone Marrow Concentrate into the painful disc/discs.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

A high index of suspicion for discogenic pain, i.e. painful degenerative discs with or without contained protrusions
Age greater than 18 and less than 70 years
Maintained intervertebral disc heights of at least 50%
Pain not generated from facet joints, sacro-iliac joints or any pathology other than discogenic origin.
Pain is not responsive to conservative treatment measures (oral medications, epidural steroid injections, physical therapy)

Key exclusion criteria (10 listed)

Disc extrusions, disc sequestrations, severe spinal stenosis, or severe disc degeneration with grade 5 Pfirmann index or with Modic 3 level change.
Patient refusal
Presence of a known bleeding disorder
Pregnancy
Systemic or local infection

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Intradiscal PRP & BMC InjectionsThe intervention to be studied is the intradiscal delivery of autologous Platelet Rich Plasma (PRP) or bone marrow concentrate (BMC) into the nucleus pulposus of the disrupted disc(s).	Procedure or surgery	Bone Marrow Aspirate Injection, Platelet Rich Plasma Injection, Trigger Point Needling

Primary outcome

Worsening of Disc Pathology with Injection of Biologics
Time frame: 24 weeks post procedure
Pre and post op discs will be examined and compared for worsening pathology.
Improvement in Disc Pain with Injection of Biologics
Time frame: 24 weeks post procedure
Pre and post op Pain will be measured and compared by Numeric Rating Scale (NRS) Numeric Pain Rating Scale (NRS): Measured from 0-10, 0 minimum score (better outcome) and 10 maximum score (worse outcome) Oswestry Low back disability (ODS): Measured from 0-50, 0 minimum score and 10 maximum score. The numbers are then calculated into percentages between 0% (minimum disability- better outcome)-100% (maximum disability- worse outcome) NASS Patient satisfaction Index (NASS): Measured from 0-4, 0 (better outcome) and 4 (worse outcome)
Improvement in Function in Patients with Injection of Biologics
Time frame: 24 weeks post procedure
Pre and post op function will be measured and compared by Oswestry Disability Index (ODI)

4 secondary outcomes

Patient Satisfaction
Time frame: Pre injection, 1 month post op, 3 months post op, 6 months post op, 1 year.
Hospitalization
Time frame: Pre injection, 1 month post op, 3 months post op, 6 months post op, 1 year.
Spine Surgery
Time frame: Pre injection, 1 month post op, 3 months post op, 6 months post op, 1 year.
Medications
Time frame: Pre injection, 1 month post op, 3 months post op, 6 months post op, 1 year.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2021.
Background: PubMed 22136441Mehra M, Hill K, Nicholl D, Schadrack J. The burden of chronic low back pain with and without a neuropathic component: a healthcare resource use and cost analysis. J Med Econ. 2012;15(2):245-52. doi: 10.3111/13696998.2011.642090. Epub 2011 Dec 5.
Background: PubMed 19847321Zhang YG, Guo TM, Guo X, Wu SX. Clinical diagnosis for discogenic low back pain. Int J Biol Sci. 2009 Oct 13;5(7):647-58. doi: 10.7150/ijbs.5.647.
Background: PubMed 25348151Omlor GW, Nerlich AG, Tirlapur UK, Urban JP, Guehring T. Loss of notochordal cell phenotype in 3D-cell cultures: implications for disc physiology and disc repair. Arch Orthop Trauma Surg. 2014 Dec;134(12):1673-81. doi: 10.1007/s00402-014-2097-2. Epub 2014 Oct 28.
Background: PubMed 10615986Konttinen YT, Kemppinen P, Li TF, Waris E, Pihlajamaki H, Sorsa T, Takagi M, Santavirta S, Schultz GS, Humphreys-Beher MG. Transforming and epidermal growth factors in degenerated intervertebral discs. J Bone Joint Surg Br. 1999 Nov;81(6):1058-63. doi: 10.1302/0301-620x.81b6.9321.
Background: PubMed 25653173Wang SZ, Chang Q, Lu J, Wang C. Growth factors and platelet-rich plasma: promising biological strategies for early intervertebral disc degeneration. Int Orthop. 2015 May;39(5):927-34. doi: 10.1007/s00264-014-2664-8. Epub 2015 Feb 5.
Background: PubMed 15980999Tolonen J, Gronblad M, Vanharanta H, Virri J, Guyer RD, Rytomaa T, Karaharju EO. Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor. Eur Spine J. 2006 May;15(5):588-96. doi: 10.1007/s00586-005-0930-6. Epub 2005 Jun 25.
Background: PubMed 18492486Fujita N, Imai J, Suzuki T, Yamada M, Ninomiya K, Miyamoto K, Iwasaki R, Morioka H, Matsumoto M, Chiba K, Watanabe S, Suda T, Toyama Y, Miyamoto T. Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc. Biochem Biophys Res Commun. 2008 Jul 25;372(2):367-72. doi: 10.1016/j.bbrc.2008.05.044. Epub 2008 May 19.
Background: PubMed 22461800Civinini R, Macera A, Nistri L, Redl B, Innocenti M. The use of autologous blood-derived growth factors in bone regeneration. Clin Cases Miner Bone Metab. 2011 Jan;8(1):25-31.
Background: PubMed 14691563Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 2004 Jan;91(1):4-15. doi: 10.1160/TH03-07-0440.
Background: PubMed 18298653Hoogendoorn RJ, Lu ZF, Kroeze RJ, Bank RA, Wuisman PI, Helder MN. Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J Cell Mol Med. 2008 Dec;12(6A):2205-16. doi: 10.1111/j.1582-4934.2008.00291.x. Epub 2008 Feb 24.
Background: PubMed 15564925Masuda K, Oegema TR Jr, An HS. Growth factors and treatment of intervertebral disc degeneration. Spine (Phila Pa 1976). 2004 Dec 1;29(23):2757-69. doi: 10.1097/01.brs.0000146048.14946.af.
Background: PubMed 24469887Pirvu TN, Schroeder JE, Peroglio M, Verrier S, Kaplan L, Richards RG, Alini M, Grad S. Platelet-rich plasma induces annulus fibrosus cell proliferation and matrix production. Eur Spine J. 2014 Apr;23(4):745-53. doi: 10.1007/s00586-014-3198-x. Epub 2014 Jan 28.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Annu Navani, MD principal investigator

Comprehensive Spine & Sports Center

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Intradiscal PRP & BMC Injections in people with Internal Disc Disruption, run by Annu Navani at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Worsening of Disc Pathology with Injection of Biologics (time frame: 24 weeks post procedure). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04102761, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2021.