Ultrasound Guided Platelet Rich Plasma Injections for Post Traumatic Greater Occipital Neuralgia

NCT04051203 | Completed Phase 1 DMC

• 1 other identifier: REB18-1368
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized controlled trial, assessing the effect of a single platelet rich plasma (PRP) injection in post traumatic (concussive) greater occipital neuralgia. This study will compare the effects of a single PRP injection to injection with steroid and anesthetic. There will also be a third arm to the study, in which patients will receive an injection with normal saline. This study will assess the severity and frequency of headache symptoms before and after receiving the injection.

Conditions

Occipital Neuralgia; Headache

Keywords

GON; greater occipital neuralgia; post traumatic headache; post concussive headache

Outcome Measures

Primary Outcomes (2)

• Evaluate the feasibility of platelet-rich plasma for patients with post-traumatic greater occipital neuralgia

  The feasibility will be determined based on recruitment (greater than 30% of those screened eligible), attendance (70% intervention appointment attendance), retention (70% complete study protocol), and the acceptability of the protocol

  Screening, pre-injection to 3-months post injection

• Evaluate the safety profile of platelet-rich plasma for the treatment of post-traumatic greater occipital neuralgia

  Safety will be determined based on adverse reactions monitored through daily headache diary reporting and communication with the study team

  from immediately post-injection to 3-months, daily recording

Secondary Outcomes (4)

• Change in headache severity as measured by the Numerical Pain Raiting Scale (NPRS)

  Pre-injection to 3 months post injection, daily recording.

• Change in headache frequency (days per month with headache).

  Pre-injection to 3 months post injection, daily recording.

• Headache Impact Test-6

  Pre-injection, 1 month, and 3 month time points.

• Quality of Life in Following Brain Injury Questionnaire

  Pre-injection, 1 month, and 3 month follow-ups.

Study Arms (3)

Autologous Platelet Rich Plasma Injection

EXPERIMENTAL

PRP contains high concentrations of platelets, growth factors, and anti-inflammatory molecules.

Biological: Autologous Platelet Rich Plasma Injection

Standard Treatment

ACTIVE COMPARATOR

Steroid and anesthetic injection: the clinical standard.

Drug: Depo-Medrol and lidocaine

Normal Saline

PLACEBO COMPARATOR

Placebo injection, with no known treatment effects.

Other: Normal Saline

Interventions

Autologous Platelet Rich Plasma Injection BIOLOGICAL

60mL of blood will be drawn from the antecubital vein and processed via centrifugation. Samples will be centrifuged as per manufacturer instructions, yielding 5mL of PRP.

Autologous Platelet Rich Plasma Injection

Depo-Medrol and lidocaine DRUG

Steroid injections will be prepared to include 20mg Depo-Medrol and 2mL 2% lidocaine.

Standard Treatment

Normal Saline OTHER

2mL normal saline.

Normal Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible participants will be males or females at least 18 years of age who suffer from post-traumatic headaches secondary to GON. Patients must fulfill the ICHD-3 criteria in establishing a diagnosis of GON. This diagnosis will be established by an experienced Physiatrist with extensive experience in headache and related disorders. To meet this criteria, patients must have experienced previous successful temporary relief with local anesthetic or steroid injection surrounding the GON in the past, but have not received local steroid injection within past 3 months. Pre-treatment numerical pain rating scale for daily headache intensity must be ≥4/10, with a headache frequency ≥10 days/month. Possible secondary causes of ON must be ruled out with reasonable level of investigation prior to enrollment.

You may not qualify if:

• Inability to provide informed consent; history of surgery in the occipital region; unstable psychiatric or medical condition; rheumatologic or inflammatory disorders; widespread neurologic disorders (eg. MS); coagulopathy; immunosuppression; active cancer; herpes zoster infection in last 6 months; pregnancy; steroid or other local GON or LON infiltration in past 3 months.

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

Foothills Medical Center, Main Floor Special Services

Calgary, Alberta, T2N2T9, Canada

Location

Related Publications (38)

• Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.

  PMID: 29368949 BACKGROUND

• Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation. 2007;22(5):341-53.

  PMID: 18162698 BACKGROUND

• Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, Agrawal A, Adeleye AO, Shrime MG, Rubiano AM, Rosenfeld JV, Park KB. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018 Apr 27;130(4):1080-1097. doi: 10.3171/2017.10.JNS17352. Print 2019 Apr 1.

  PMID: 29701556 BACKGROUND

• Coronado VG, Xu L, Basavaraju SV, McGuire LC, Wald MM, Faul MD, Guzman BR, Hemphill JD; Centers for Disease Control and Prevention (CDC). Surveillance for traumatic brain injury-related deaths--United States, 1997-2007. MMWR Surveill Summ. 2011 May 6;60(5):1-32.

  PMID: 21544045 BACKGROUND

• Ponsford JL, Downing MG, Olver J, Ponsford M, Acher R, Carty M, Spitz G. Longitudinal follow-up of patients with traumatic brain injury: outcome at two, five, and ten years post-injury. J Neurotrauma. 2014 Jan 1;31(1):64-77. doi: 10.1089/neu.2013.2997.

  PMID: 23889321 BACKGROUND

• Lundin A, de Boussard C, Edman G, Borg J. Symptoms and disability until 3 months after mild TBI. Brain Inj. 2006 Jul;20(8):799-806. doi: 10.1080/02699050600744327.

  PMID: 17060147 BACKGROUND

• Hoffman JM, Lucas S, Dikmen S, Braden CA, Brown AW, Brunner R, Diaz-Arrastia R, Walker WC, Watanabe TK, Bell KR. Natural history of headache after traumatic brain injury. J Neurotrauma. 2011 Sep;28(9):1719-25. doi: 10.1089/neu.2011.1914. Epub 2011 Aug 29.

  PMID: 21732765 BACKGROUND

• Hammond SR, Danta G. Occipital neuralgia. Clin Exp Neurol. 1978;15:258-70.

  PMID: 756019 BACKGROUND

• Dougherty C. Occipital neuralgia. Curr Pain Headache Rep. 2014 May;18(5):411. doi: 10.1007/s11916-014-0411-x.

  PMID: 24737457 BACKGROUND

• Ward JB. Greater occipital nerve block. Semin Neurol. 2003 Mar;23(1):59-62. doi: 10.1055/s-2003-40752.

  PMID: 12870106 BACKGROUND

• Anthony M. Headache and the greater occipital nerve. Clin Neurol Neurosurg. 1992;94(4):297-301. doi: 10.1016/0303-8467(92)90177-5.

  PMID: 1335856 BACKGROUND

• Choi I, Jeon SR. Neuralgias of the Head: Occipital Neuralgia. J Korean Med Sci. 2016 Apr;31(4):479-88. doi: 10.3346/jkms.2016.31.4.479. Epub 2016 Mar 9.

  PMID: 27051229 BACKGROUND

• Kuhn WF, Kuhn SC, Gilberstadt H. Occipital neuralgias: clinical recognition of a complicated headache. A case series and literature review. J Orofac Pain. 1997 Spring;11(2):158-65.

  PMID: 10332322 BACKGROUND

• Laver L, Marom N, Dnyanesh L, Mei-Dan O, Espregueira-Mendes J, Gobbi A. PRP for Degenerative Cartilage Disease: A Systematic Review of Clinical Studies. Cartilage. 2017 Oct;8(4):341-364. doi: 10.1177/1947603516670709. Epub 2016 Sep 1.

  PMID: 28317389 BACKGROUND

• Sampson S, Gerhardt M, Mandelbaum B. Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med. 2008 Dec;1(3-4):165-74. doi: 10.1007/s12178-008-9032-5.

  PMID: 19468902 BACKGROUND

• Anitua E, Sanchez M, Orive G, Andia I. The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials. 2007 Nov;28(31):4551-60. doi: 10.1016/j.biomaterials.2007.06.037. Epub 2007 Jul 30.

  PMID: 17659771 BACKGROUND

• Park GY, Kwon DR. Platelet-rich plasma limits the nerve injury caused by 10% dextrose in the rabbit median nerve. Muscle Nerve. 2014 Jan;49(1):56-60. doi: 10.1002/mus.23863. Epub 2013 Sep 20.

  PMID: 23558771 BACKGROUND

• Farrag TY, Lehar M, Verhaegen P, Carson KA, Byrne PJ. Effect of platelet rich plasma and fibrin sealant on facial nerve regeneration in a rat model. Laryngoscope. 2007 Jan;117(1):157-65. doi: 10.1097/01.mlg.0000249726.98801.77.

  PMID: 17202946 BACKGROUND

• Sariguney Y, Yavuzer R, Elmas C, Yenicesu I, Bolay H, Atabay K. Effect of platelet-rich plasma on peripheral nerve regeneration. J Reconstr Microsurg. 2008 Apr;24(3):159-67. doi: 10.1055/s-2008-1076752. Epub 2008 Apr 30.

  PMID: 18452111 BACKGROUND

• Ding XG, Li SW, Zheng XM, Hu LQ, Hu WL, Luo Y. The effect of platelet-rich plasma on cavernous nerve regeneration in a rat model. Asian J Androl. 2009 Mar;11(2):215-21. doi: 10.1038/aja.2008.37. Epub 2009 Jan 19.

  PMID: 19151738 BACKGROUND

• Giannessi E, Coli A, Stornelli MR, Miragliotta V, Pirone A, Lenzi C, Burchielli S, Vozzi G, De Maria C, Giorgetti M. An autologously generated platelet-rich plasma suturable membrane may enhance peripheral nerve regeneration after neurorraphy in an acute injury model of sciatic nerve neurotmesis. J Reconstr Microsurg. 2014 Nov;30(9):617-26. doi: 10.1055/s-0034-1372483. Epub 2014 May 16.

  PMID: 24838385 BACKGROUND

• Sanchez M, Anitua E, Delgado D, Prado R, Sanchez P, Fiz N, Guadilla J, Azofra J, Pompei O, Orive G, Ortega M, Yoshioka T, Padilla S. Ultrasound-guided plasma rich in growth factors injections and scaffolds hasten motor nerve functional recovery in an ovine model of nerve crush injury. J Tissue Eng Regen Med. 2017 May;11(5):1619-1629. doi: 10.1002/term.2079. Epub 2015 Sep 7.

  PMID: 26876895 BACKGROUND

• Zheng C, Zhu Q, Liu X, Huang X, He C, Jiang L, Quan D, Zhou X, Zhu Z. Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro. J Tissue Eng Regen Med. 2016 May;10(5):428-36. doi: 10.1002/term.1756. Epub 2013 May 31.

  PMID: 23723151 BACKGROUND

• Anjayani S, Wirohadidjojo YW, Adam AM, Suwandi D, Seweng A, Amiruddin MD. Sensory improvement of leprosy peripheral neuropathy in patients treated with perineural injection of platelet-rich plasma. Int J Dermatol. 2014 Jan;53(1):109-13. doi: 10.1111/ijd.12162. Epub 2013 Oct 29.

  PMID: 24168291 BACKGROUND

• Sanchez M, Yoshioka T, Ortega M, Delgado D, Anitua E. Ultrasound-guided platelet-rich plasma injections for the treatment of common peroneal nerve palsy associated with multiple ligament injuries of the knee. Knee Surg Sports Traumatol Arthrosc. 2014 May;22(5):1084-9. doi: 10.1007/s00167-013-2479-y. Epub 2013 Mar 22.

  PMID: 23519544 BACKGROUND

• Raeissadat SA, Karimzadeh A, Hashemi M, Bagherzadeh L. Safety and efficacy of platelet-rich plasma in treatment of carpal tunnel syndrome; a randomized controlled trial. BMC Musculoskelet Disord. 2018 Feb 13;19(1):49. doi: 10.1186/s12891-018-1963-4.

  PMID: 29433485 BACKGROUND

• Malahias MA, Johnson EO, Babis GC, Nikolaou VS. Single injection of platelet-rich plasma as a novel treatment of carpal tunnel syndrome. Neural Regen Res. 2015 Nov;10(11):1856-9. doi: 10.4103/1673-5374.165322.

  PMID: 26807124 BACKGROUND

• Uzun H, Bitik O, Uzun O, Ersoy US, Aktas E. Platelet-rich plasma versus corticosteroid injections for carpal tunnel syndrome. J Plast Surg Hand Surg. 2017 Oct;51(5):301-305. doi: 10.1080/2000656X.2016.1260025. Epub 2016 Dec 6.

  PMID: 27921443 BACKGROUND

• Wu YT, Ho TY, Chou YC, Ke MJ, Li TY, Huang GS, Chen LC. Six-month efficacy of platelet-rich plasma for carpal tunnel syndrome: A prospective randomized, single-blind controlled trial. Sci Rep. 2017 Dec;7(1):94. doi: 10.1038/s41598-017-00224-6. Epub 2017 Mar 7.

  PMID: 28273894 BACKGROUND

• Shim JH, Ko SY, Bang MR, Jeon WJ, Cho SY, Yeom JH, Shin WJ, Kim KH, Shim JC. Ultrasound-guided greater occipital nerve block for patients with occipital headache and short term follow up. Korean J Anesthesiol. 2011 Jul;61(1):50-4. doi: 10.4097/kjae.2011.61.1.50. Epub 2011 Jul 21.

  PMID: 21860751 BACKGROUND

• Kosinski M, Bayliss MS, Bjorner JB, Ware JE Jr, Garber WH, Batenhorst A, Cady R, Dahlof CG, Dowson A, Tepper S. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003 Dec;12(8):963-74. doi: 10.1023/a:1026119331193.

  PMID: 14651415 BACKGROUND

• Nachit-Ouinekh F, Dartigues JF, Henry P, Becg JP, Chastan G, Lemaire N, El Hasnaoui A. Use of the headache impact test (HIT-6) in general practice: relationship with quality of life and severity. Eur J Neurol. 2005 Mar;12(3):189-93. doi: 10.1111/j.1468-1331.2004.00934.x.

  PMID: 15693807 BACKGROUND

• Palamar D, Uluduz D, Saip S, Erden G, Unalan H, Akarirmak U. Ultrasound-guided greater occipital nerve block: an efficient technique in chronic refractory migraine without aura? Pain Physician. 2015 Mar-Apr;18(2):153-62.

  PMID: 25794201 BACKGROUND

• Zipfel J, Kastler A, Tatu L, Behr J, Kechidi R, Kastler B. Ultrasound-Guided Intermediate Site Greater Occipital Nerve Infiltration: A Technical Feasibility Study. Pain Physician. 2016 Sep-Oct;19(7):E1027-34.

  PMID: 27676673 BACKGROUND

• Gul HL, Ozon AO, Karadas O, Koc G, Inan LE. The efficacy of greater occipital nerve blockade in chronic migraine: A placebo-controlled study. Acta Neurol Scand. 2017 Aug;136(2):138-144. doi: 10.1111/ane.12716. Epub 2016 Dec 2.

  PMID: 27910088 BACKGROUND

• Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9.

  PMID: 11690728 BACKGROUND

• Stone JE, Campbell C, Tabor JB, Bonfield S, Machan M, Shan RLP, Debert CT. Ultrasound guided platelet rich plasma injections for post-traumatic greater occipital neuralgia following concussion: a pilot randomized controlled trial. Front Neurol. 2024 Jun 7;15:1400057. doi: 10.3389/fneur.2024.1400057. eCollection 2024.

  PMID: 38911584 DERIVED

• Stone JE, Fung TS, Machan M, Campbell C, Shan RLP, Debert CT. Ultrasound-guided platelet-rich plasma injections for post-traumatic greater occipital neuralgia: study protocol for a pilot randomized controlled trial. Pilot Feasibility Stud. 2021 Jun 22;7(1):130. doi: 10.1186/s40814-021-00867-3.

  PMID: 34158124 DERIVED

MeSH Terms

Conditions

Headache; Post-Traumatic Headache

Interventions

Methylprednisolone Acetate; Lidocaine; Saline Solution

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All members of the study will be blinded (participants and healthcare practioners) except for the study coordinator.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized controlled trial, participants are randomly assigned to one of three groups; an autologous PRP injection, a steroid injection, or normal saline.

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: August 9, 2019
• Study Start: February 1, 2019
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: February 6, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)