Pulsed Radiofrequency Combined With Platelet-Rich Plasma Applied to the Sphenopalatine Ganglion in Treating Episodic Cluster Headache

Efficacy and Safety of Pulsed Radiofrequency Combined With Platelet-Rich Plasma Applied to the Sphenopalatine Ganglion in Treating Episodic Cluster Headache: A Study Protocol for a Multi-Center, Prospective, Open-Label, Propensity Score Match Cohort Study

Cluster headache (CH) is one of the most severe pain accompanied by ipsilateral autonomic symptoms such as lacrimation and conjunctival injection. CH can be categorized into episodic cluster headache (ECH), chronic cluster headache (CCH), and probable CH. Intervention for CH requires a multifaceted and early approach and varies due to the heterogeneity of patients, which makes it difficult to formulate appropriate treatment plan, and the minimally invasive interventional therapy between drug and surgical treatment is still worth looking forward to.

The pterygopalatine ganglion, also known as SPG, is a essential proportion in activation of cortical structures and plays an important role in the pathogenesis of CH attacks, which makes it the potential therapeutic target in drug-resistant CH. Percutaneous pulsed radiofrequency (PRF) at SPG is a minimally destructive treatment which shows efficacy, safety, and repeatedly efficacy for refractory CH. PRF is a reliable alternative with few neurological side effects and complications for patients who have not responded to conservative treatment. However, the long term pain relieve is not satisfying. Platelet-rich plasma (PRP) is an autologous blood-derived product of 3 times concentrated platelet above average levels, which contains many growth factors, cytokines, chemokine, and cell-adhesion molecules, therefore function in the activation and synthesis of healing process, tissue proliferation and regeneration. Researches by Michno etc. and Giaccari etc. have proved that PRP combined with PRF therapy may provide more effective outcome than PRF alone in treatment of neuralgia, but whether the combined therapy can improve the efficacy of CH treatment is not clear. ECH occurs in 90% of the CH patients. The investigators assume that PRP combined with PRF acting on SPG might have better therapeutic effect on ECH than PRF alone, by giving combined treatment or PRF therapy alone according to patients willingness, the investigators plan on conducting this prospective trail to compare the clinical efficacy and safety of PRP combined with PRF versus PRF alone.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain Management; Cluster Headache; Episodic Cluster Headache

• Study Type: Observational
• Enrollment (Estimated): 242

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Beijing Tiantan Hospital
      • Contact: Fang Luo, M.D.; Phone Number: 86 13611326978; Email: 13611326978@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Suitable participants will be screened at the pain management centre of Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University in Beijing, China; Department of Pain Management, Henan Provincial People's Hospital, Henan, China; Department of Pain Management, Huadong Hospital, Fudan University, Shanghai. to participate in the study.

Description

Inclusion Criteria:

1. The diagnosis of ECH is confirmed according to the diagnostic criteria of the International Classification of Headache Disorders third edition 3 (Table 2), and the patient is within five days of the current cluster period；
2. The patient's age is between 18 and 70 years;
3. Patients have had ≥2 bouts previously, ≥4 typical (treated or untreated) attacks per week and usual bouts should last 4 weeks;
4. The patient's pain condition remains the same after preventive therapy with drugs available in our hospital such as verapamil, topiramate, lithium or steroids, or there is a reduction of less than 50% in the intensity and frequency of headache attacks, the duration of each attack and the dosage of auxiliary analgesic drugs used.

Exclusion Criteria:

1. Have atypical features: absence of cranial autonomic symptoms, post-traumatic onset, cluster-tic syndrome;
2. Abnormalities in blood measurements, liver and kidney function, blood glucose, coagulation, electrocardiography or chest radiography;
3. Infection at the puncture site;
4. Previous mental illness;
5. Previous history of narcotic drug abuse;
6. Prior anticoagulant or antiplatelet therapy;
7. An implantable pulse generator;
8. Previous history of invasive treatments such as pterygopalatine ganglion radiofrequency thermocoagulation and chemical destruction;
9. Current pregnancy or breast feeding.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pulse Radiofrequency combined with Platelet Rich Plasma; The pulse treatment generator will be set to the automatic pulsed radiofrequency mode, with a temperature of 42°C, pulse frequency of 2Hz, pulse width of 20ms and treatment duration of 360s. After removing the radiofrequency electrode, 2 ml of LP-PRP mixture will be injected slowly into the sphenopalatine ganglion. Additional analgesics will be administered for participants' comfort during and after the procedure. If the patients were not satisfied with the outcome after one month, other treatment options will be available.
Pulse Radiofrequency alone; The pulse treatment generator will be set to the automatic pulsed radiofrequency mode, with a temperature of 42°C, pulse frequency of 2Hz, pulse width of 20ms and treatment duration of 360s. Patient from this group will not receive PRP injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in the weekly frequency of cluster headache attacks	The overall mean change from baseline in the weekly frequency of cluster headache attacks across weeks 1 through 3	At 1 week, 2 weeks, 3 weeks after the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in the weekly frequency of cluster headache attacks	the overall mean change from baseline in the weekly frequency of cluster headache attacks	At 1day, 3days, 1week, 2weeks, 1month, 3months, 6months and 1year after the operation
the percentage of patients with a reduction of at least 50% in the weekly frequency of cluster headache attacks	the percentage of patients with a reduction from baseline of at least 50% in the weekly frequency of cluster headache attacks	At 1day, 3days, 1week, 2weeks, 1month, 3months, 6months and 1year after the operation.
the degree of pain	the degree of pain during headache attacks (NRS scores)	At 1day, 3days, 1week, 2weeks, 1month, 3months, 6months and 1year after the operation.
the duration of each headache attack	the duration of each headache attack	At 1day, 3days, 1week, 2weeks, 3 weeks, 1month, 3months, 6months and 1year after the procedure.
dose of auxiliary analgesic drugs	the dose of auxiliary analgesic drugs taken	At 1day, 3days, 1week, 2weeks, 3 weeks, 1month, 3months, 6months and 1year after the procedure.
self-rated patient satisfaction	the self-rated patient satisfaction, from 0 point for unsatisfied to 10 points for very satisfied.	At 1day, 3days, 1week, 2weeks, 3 weeks, 1month, 3months, 6months and 1year after the procedure.
WHOQOL-BREF	the degree of patient satisfaction measured by WHOQOL-BREF (World Health Organization Quality of Life Questionnaire).	At 1day, 3days, 1week, 2weeks, 3 weeks, 1month, 3months, 6months and 1year after the procedure.
adverse events	For intraoperative AEs, the occurrence of puncture pain, headache, dizziness, nausea, vomiting, facial haematoma and other effects will be recorded. For postoperative AEs, headache, dizziness, facial numbness and other effects will also be recorded.	At 1day, 3days, 1week, 2weeks, 3 weeks, 1month, 3months, 6months and 1year after the procedure.

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Huadong Hospital; People's Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: March 12, 2025
• First Submitted That Met QC Criteria: March 12, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Pain management; Pulsed Radiofrequency; Episodic Cluster Headache; Platlet-rich Plasma
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Trigeminal Autonomic Cephalalgias; Headache; Cluster Headache
• Other Study ID Numbers: KY 2023-263-03-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No