Treatment of Atypical Resistant Facial Pain

NCT ID: NCT07250984

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 10 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-11-03
• Study Completion Date: 2026-12-03

Brief Summary

Facial pain in the trigeminal nerve region, which is not a migraine headache is often very persistent and difficult to treat. Research findings suggest that, similar to the mechanisms of migraine headache, the increased concentration of calcitonin gene-related peptide (CGRP) plays an important role in the mechanisms of facial pain.

Therefore, the hypothesis is that intravenous administration of ACMP will similarly disrupt central sensitization in facial pain as it does in migraine headaches.

Detailed Description

Facial pain in the trigeminal nerve region, which is not a migraine headache (e.g., cluster headaches, trigeminal neuralgia, burning mouth syndrome), is often very persistent and difficult to treat. Despite the use of all available treatment methods is often unsuccessful. Research findings suggest that, similar to the mechanisms of migraine headache, the increased concentration of calcitonin gene-related peptide (CGRP) plays an important role in the mechanisms of facial pain. Trigeminal neuralgia has already been treated with intravenous administration of anti-CGRP monoclonal antibodies (ACMP), such as eptinezumab.

In facial pain, as in chronic migraine, both peripheral and central nervous system sensitization can occur. Central sensitization is a poorly understood biological phenomenon, although some mechanisms are known. According to current knowledge and clinical experience, CGRP likely plays a central role in central sensitization that occurs in facial pain. It is known that in chronic migraine, the concentration of CGRP in the blood is elevated.

The peripheral mechanism of sensitization is not entirely clear, but it is likely that the peripheral part of the autonomic nervous system, specifically the parasympathetic system, plays an important role. The trigeminovascular reflex, a consequence of the autonomic segmental reflex, causes peripheral sensitization. Neurogenic inflammation also occurs. Neurogenic inflammation in the meninges further sensitizes the trigeminal nerve fibers.

CGRP is important for regulating physiological processes in the human body. It is also important for the sensitization of the peripheral nervous system, which can lead to central sensitization and create a vicious cycle. Central sensitization is a source of pro-inflammatory factors that promote neurogenic inflammation.

The level of CGRP in the body depends on its production and removal from the blood. ACMP effectively inactivate CGRP, thus reducing the number of migraine episodes and their intensity. Therefore, we hypothesize that intravenous administration of ACMP will similarly disrupt central sensitization in facial pain as it does in migraine headaches. Pharmacokinetic studies with eptinezumab have shown that intravenous administration of eptinezumab leads to an immediate peak concentration of ACMP, while subcutaneous administration reaches this effect only after several days. Since the biological availability of ACMP is significantly higher in the first few days, this may lead to the most effective reduction in CGRP influx and a probable clinical reduction in facial pain.

There are some attempts in the literature to treat cluster headaches with ACMP, but there is no data available for other syndromes.

The study will take place at the Chronic Pain Treatment Department of the Clinical Department of Anesthesiology and Intensive Care at the University Medical Centre (UKC) Ljubljana and will be designed as a multidisciplinary study (neurology and anesthesiology). 10 patients with facial pain in the trigeminal nerve region who do not have a migraine headache (e.g., cluster headaches, trigeminal neuralgia, burning mouth syndrome) and who have not responded to conventional treatment approaches will be included. Each participant will be individually assessed and invited to participate in the study, followed by an explanatory conversation. After obtaining written consent, an intravenous line will be established, and standard monitoring (non-invasive blood pressure, pulse oximeter, oximetry) will be applied. A venous blood sample will be taken, followed by a 30-minute infusion of eptinezumab. A venous blood sample and the eptinezumab dose will be repeated after three months. CGRP levels, pro-inflammatory cytokines, and specific biomarkers will be monitored, before the and after three months of drug administration .

Conditions

Facial Pain

Keywords

facial pain; CGRP; intravenous ACMP

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

intravenous administration of ACMP

30-minute infusion of 100 mg of eptinezumab, repeated after three months

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• facial pain

Exclusion Criteria

• psychiatric disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alenka Spindler-Vesel

OTHER

Sponsor Role: lead

Responsible Party

Alenka Spindler-Vesel

Assoc. Prof., MD

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Pain Therapy Clinic of University Medical Centre Ljubljana

Ljubljana, , Slovenia

Countries

Slovenia

Other Identifiers

0120-331/2024-2711-8

Identifier Type: -

Identifier Source: org_study_id