A Study to Investigate the Efficacy of Pain Reduction With Cryoneurolysis Compared With Sham-treatment in Adults With Trigeminal Neuralgia (CryoGem)

• ClinicalTrials.gov Identifier: NCT06213155
• Recruitment Status: Recruiting
• First Posted: January 19, 2024
• Last Update Posted: January 22, 2024
• Sponsor: St. Olavs Hospital
• Information provided by (Responsible Party): St. Olavs Hospital

Tracking Information

• First Submitted Date: January 9, 2024
• First Posted Date: January 19, 2024
• Last Update Posted Date: January 22, 2024
• Estimated Study Start Date: January 2024
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2024)

• Average daily pain [ Time Frame: Weeks 3 - 4 post-intervention compared to baseline ]
  Difference in number of treatment responders (≥ 75% reduction in the mean average daily pain intensity on a NRS score) at weeks 3 - 4 post-intervention for paroxysmal pain corresponding to the treated branch compared to baseline in the treatment versus the sham group.
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Week 1-4 ]
  Occurrence of treatment-emergent adverse events and serious adverse events.

Original Primary Outcome Measures (submitted: January 9, 2024)

• Average daily pain [ Time Frame: Weeks 3 - 4 post-intervention compared to baseline ]
  Difference in number of treatment responders (≥ 75% reduction in the mean average daily pain intensity on a NRS score) at weeks 3 - 4 post-intervention for paroxysmal pain corresponding to the treated branch compared to baseline in the treatment versus the sham group.
• Safety of the treatment [ Time Frame: Week 1-4 ]
  Occurrence of treatment-emergent adverse events and serious adverse events.

Current Secondary Outcome Measures (submitted: January 9, 2024)

• 50% responders [ Time Frame: Weeks 3 - 4 post-intervention compared to baseline ]
  Difference in number of treatment responders (≥ 50% reduction in the mean average daily pain intensity on a Numeric Rating Scale (NRS) score at weeks 3 - 4 post-intervention for paroxysmal pain corresponding to the treated branch compared to baseline) in the treatment versus the sham group.
• 100% responders [ Time Frame: Weeks 3 - 4 post-intervention compared to baseline ]
  Difference in number of complete responders (100% reduction in the mean average daily pain intensity on a NRS score at weeks 3 - 4 post-intervention for paroxysmal pain corresponding to the treated branch compared to baseline) in the active arm versus the sham arm.
• Patient Global Impression of Change (PGI-C) scale responders (a PGI- C responder is defined as having a response of "much improved" or "very much improved" at week 4.) [ Time Frame: Week 4 ]
  Difference in number of PGI-C responders corresponding to the treated branch at week 4 in the active arm versus sham arm.
• Barrow Institute of (BNI- P) responders (a clinically significant response is defined as having BNI I - BNI IIIb at week 4). [ Time Frame: Week 4 in the active arm versus sham arm. ]
  Difference in number of clinically significant BNI-P responders at week 4 in the active arm versus sham arm.
• Barrow Institute of (BNI- P) excellent responders (excellent response is defined as having BNI I - BNI II at week 4). [ Time Frame: Weeks 3 - 4 post-intervention compared to baseline ]
  Difference in number of excellent BNI-P responders at week 4 in the active arm versus sham arm.
• Penn Facial Pain Scale- Revised (PENN-FPS-R) score. [ Time Frame: Week 4 post-intervention compared to baseline ]
  Difference in reduction of PENN-FPS-R from baseline to week 4 in the active arm versus sham arm.
• Change in mean average daily pain intensity NRS score (ADP) in the active versus sham arm. [ Time Frame: Weeks 3 - 4 post-intervention compared to baseline ]
  Difference in reduction mean average daily pain intensity NRS score (ADP) corresponding to the treated branch at weeks 3 - 4 compared to baseline in the active arm versus the sham arm.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Investigate the Efficacy of Pain Reduction With Cryoneurolysis Compared With Sham-treatment in Adults With Trigeminal Neuralgia
• Official Title: A Randomized, Parallel Arm, Sham-controlled, Double-blinded, Investigator-initiated Trial to Investigate the Safety and Efficacy of Percutaneous Peripheral Cryoneurolysis Therapy in Medically Refractory Trigeminal Neuralgia: a Pilot Study

Brief Summary

The CryoGem Trial is a research study that tests a freezing technique called cryoneurolysis to see if it helps relieve pain in adults with trigeminal neuralgia. Trigeminal neuralgia is a condition that causes severe facial pain. In this study, we want to find out if the freezing technique is effective and safe. We will do this by comparing two groups of adults with trigeminal neuralgia. One group will receive the actual treatment, while the other group will receive a fake treatment called a sham. Neither the participants nor the assessors will know which group they are in (this is called a blinded study). For the next four weeks, participants in both groups will continue recording their headaches without knowing which treatment they are receiving. After this initial period, there will be an extension period where all participants can receive treatment as needed for up to two years. The results of this study will help us decide if the freezing technique is a viable treatment option for trigeminal neuralgia. Our main goal is to see how many people in each group have a significant reduction in pain (at least 75% less pain). We will also record other important information about the participants.

We are looking to recruit up to 24 adults with trigeminal neuralgia to take part in this study. All participants will keep a daily diary for two weeks to track their headaches before starting the treatment. Then, they will be randomly assigned to either the treatment group or the sham group.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Trigeminal Neuralgia

Intervention

• Device: Cryoneurolysis
  Cryoneurolysis
• Device: Stimulation
  Stimulation

Study Arms

• Experimental: Cryoneurolysis
  Intervention: Device: Cryoneurolysis
• Sham Comparator: Stimulation
  Intervention: Device: Stimulation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 9, 2024): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2026
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Participant must be 18 years at the time of signing the informed consent
2. A diagnosis of primary (classic and idiopathic) trigeminal neuralgia affecting the mandibular and/or maxillary division, verified by a neurologist
3. Ability to subclassify the trigeminal neuralgia according to the The International Classification of Headache Disorders, 3rd edition, i.e. sufficient magnetic resonance (MR) evaluation is mandatory
4. History of minimum mean of three trigeminal neuralgia related pain paroxysms per day last 4 weeks
5. History of minimum average daily pain intensity NRS score (ADP) of 4 to10 last 4 weeks
6. In baseline minimum average daily pain intensity NRS score (ADP) of 4 to 10
7. In baseline minimum mean of three trigeminal neuralgia related pain paroxysms per day

8. Treatment refractory as defined in this study as failure to respond, pending an adequate trial in the opinion of the investigator, contraindications or intractable side effect to one of two medications:

   1. Carbamazepine
   2. Oxcarbazepine
9. Unaltered prophylactic TN medication regime 2 weeks prior to baseline, and be willing to keep regime unaltered during the baseline and the blinded study period.
10. Be an appropriate candidate for the study intervention required in this study on the basis of the clinical judgment of the investigator
11. Capable of giving signed informed consent as which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

1. Diagnosed with demyelinating inflammatory disorders such as e.g. multiple sclerosis.
2. Other pain conditions, not intended to be treated in this study, that in the opinion of the investigator could interfere with study procedures, accurate pain reporting, and/or confound evaluation of study endpoints.
3. High probability of neurological deterioration due to other medical conditions, that in the opinion of the investigator may confound outcome assessment.
4. Patients exhibiting a high degree of comorbidity and/or frailty associated with reduced life expectancy or high likelihood of hospitalization, at the discretion of the investigator.
5. Other coexisting current medical conditions, including, but not limited to, bleeding diathesis and thrombophilia, that presents excess procedural risk, in the opinion of the investigator.
6. Have within 6 months of enrollment a significant untreated addiction to dependency- producing medications, alcohol, or illicit drugs.
7. Abnormal pain behavior, inappropriate medication use and/or unresolved psychiatric illness, that in the opinion of the investigator are significant enough to impact perception of pain, compliance with intervention and/or ability to evaluate treatment outcome.
8. Subject has had previous radiofrequency ablation (including non-lesional pulsed radiofrequency), balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the Gasserian ganglion.
9. Subject has had previous radiofrequency ablation (including non-lesional pulsed radiofrequency), balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of a division or branch of the trigeminal nerve being targeted in this study.
10. Facial anomaly or trauma which renders the planned procedure difficult.
11. Subject currently has an active oral or dental abscess or a local infection at the site of injection based on present symptoms.
12. Subject has been diagnosed with any major infectious processes such as osteomyelitis, or primary or secondary malignancies involving the face that have been active or required treatment in the past 6 months.
13. Current participation in another treatment study
14. Sensory deficits and/or pain configuration supporting, in the opinion of the neurologist, trigeminal neuropathy as more likely diagnosis.
15. Patients with any kind of conductive implant with contraindication for nerve stimulation according to study innervation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Irina Aschehoug; +47 72820972; irina.aschehoug@ntnu.no

• Listed Location Countries: Norway

Administrative Information

• NCT Number: NCT06213155
• Other Study ID Numbers: 630286
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: St. Olavs Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: St. Olavs Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: St. Olavs Hospital
• Verification Date: January 2024