Peripheral cryoneurolysis for adults with chronic migraine

An Open Label Pilot Study Investigating the Safety and Efficacy of a Percutaneous Peripheral Cryoneurolysis Therapy in Medically Resistant Chronic Migraine

This study will try a freezing treatment called cryoneurolysis to see if it reduces headaches in adults with chronic migraine.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: St. Olavs Hospital (Academic / other)
• Locations: 1 site (Trondheim)
• Trial ID: NCT06554886 on ClinicalTrials.gov

What this trial studies

This is a small, single-site interventional study enrolling 12 adults with chronic migraine who meet strict diagnostic and treatment-resistance criteria. Participants will record their headache burden in a diary for at least 4 weeks before a planned cryoneurolysis treatment and continue diary entries during follow-up. The main outcome is the amount of headache relief after treatment, and investigators will collect other safety and symptom data. Participants with recurring headaches may receive repeat treatments as needed for up to two years.

Who should consider this trial

Good fit: Adults aged 18 or older with ICHD-3 defined chronic migraine for at least one year, at least 8 debilitating headache days per month for 3+ months, and pharmacological resistance to multiple standard migraine therapies are the intended candidates.

Not a fit: People without chronic migraine, those who are not treatment-resistant, or those with medical contraindications to peripheral nerve cryoneurolysis are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, cryoneurolysis could provide longer-lasting headache relief and fewer migraine days for adults with pharmacologically resistant chronic migraine.

How similar studies have performed: Small case series and pilot studies of peripheral nerve cryoneurolysis and related nerve interventions have reported symptomatic benefit in some headache disorders, but large randomized evidence is limited.

Eligibility criteria

Inclusion Criteria:

1. Participant must be 18 years at the time of signing the informed consent
2. Migraine, with or without aura, fulfilling the International Classification of Headache Disorders (ICHD) III criteria 1.3. for chronic migraine at time of inclusion, verified by a neurologist
3. History of 8 debilitating headache days per month for at least 3 consecutive months. Debilitating headache is defined as headache causing serious impairment to conduct activities of daily living despite the use of pain-relief drugs with established efficacy at the recommended dose and taken early during the attack; failure of at least two different triptans is required.
4. Chronic migraine at least for a period of 1 year prior to inclusion
5. Debut of episodic migraine before the age of 50, and chronic migraine before the age of 65.
6. The condition is pharmacologically resistant as defined in EHF guidelines as lack of efficacy, lack of tolerability and/or contraindications to at least 3 of the following drug classes

   1. Antidepressant (Amitryptyline, Venlafaxine)
   2. Antiepileptic (Topiramate or Valproate)
   3. Beta-blocker (Atenol, Metropolol, Propanolol, Timolol)
   4. Calcium channel blockers (Flunarizine or Cinnarizine)
   5. Drugs acting on the CGRP pathway (Monoclonal antibodies and gepants)
   6. Angiotensin-converting enzyme inhibitors (Lisinopril) or angiotensin II receptor blocker (Candesartan)
   7. OnabotulinumtoxinA
7. Subject has had no change in type, dosage or dose frequency of preventive headache medications \< 3 months prior to baseline/screening, or a minimum of 5 half-lives, whichever is longer.
8. Subjects has not been treated with steroids orally or injections \>8 weeks (excluding steroid inhalations or topical treatments) prior to baseline and agrees to refrain from steroids orally or injections during baseline and 8 weeks post-intervention.
9. Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during baseline and 8 weeks after the intervention.
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. Subject is unable to differentiate migraine from other concomitant headaches.
2. Subject with secondary headache conditions, with the exception of medication overuse headache.
3. Subject that, in the opinion of the investigator, has had no or minimal response to more than 6 adequate trials of prophylactic migraine treatment of the following drug classes:

   1. Antidepressant (Amitryptyline, Venlafaxine)
   2. Antiepileptic (Topiramate or Valproate)
   3. Beta-blocker (Atenol, Metropolol, Propanolol, Timolol)
   4. Calcium channel blockers (Flunarizine or Cinnarizine)
   5. Drugs acting on the CGRP pathway (Monoclonal antibodies and gepants)
   6. Angiotensin-converting enzyme inhibitors (Lisinopril) or angiotensin II receptor blocker (Candesartan)
   7. OnabotulinumtoxinA
4. Subject has had a change in type, dosage or dose frequency of preventive headache medications during the baseline period.
5. Ongoing abuse of drugs (including narcotics) or alcohol.
6. More than 4 days of opioid use per month (including codeine and tramadol), and any use of barbiturates
7. 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.
8. High probability of deterioration due to other medical conditions, that in the opinion of the investigator may confound outcome assessment.
9. 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.
10. 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.
11. Anomaly or trauma which renders the planned procedure difficult.
12. Subject currently has an active abscess or a local infection at the site of intervention based on present symptoms.
13. Subject has been diagnosed with any major infectious processes such as osteomyelitis, or primary or secondary malignancies involving skull or site of intervention that have been active or required treatment in the past 6 months.
14. Patients with any kind of conductive implant with contraindication for nerve stimulation.
15. The subject is not competent to consent

Where this trial is running

Trondheim

• St. Olavs hospital — Trondheim, Norway (Recruiting)

Study contacts

• Principal investigator: Daniel F Bratbak, PhD — St. Olavs Hospital
• Study coordinator: Daniel F Bratbak, PhD

Conditions Chronic Migraine