Efficacy of Botulinum Toxin Type A in Sphenopalatine Ganglion Blockade for Treatment-Refractory Chronic Migraine: A Randomized Controlled Trial
- Trial ID
- 2024-515165-34-00
- Sponsor
- St. Olavs Hospital HF
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the study is to evaluate the **efficacy** of botulinum toxin type A administered towards the sphenopalatine ganglion (SPG) in patients with treatment-refractory **chronic migraine**. This is achieved using an image-guided surgical device (MultiGuide®). The clinical relevance of this objective lies in addressing the unmet need for effective treatment options in patients who do not respond to conventional therapies, potentially improving their quality of life and reducing the burden of chronic migraine.
Secondary objectives include the assessment of safety, feasibility, and the number of responders. Additionally, the study aims to evaluate the number of migraine days and crystal clear headache-free days, the acceptability of the treatment, and the features of migraine headache attacks such as intensity, autonomic symptoms, and duration. The use of acute medication and quality of life measures are also assessed. These secondary objectives provide a comprehensive understanding of the treatment's impact on various aspects of the patient's condition and overall well-being.
Participants
The clinical trial focuses on individuals diagnosed with **chronic migraine**, specifically targeting a population that is treatment refractory. The study includes both male and female participants, aged between 18 and 70 years. Participants are required to have a history of chronic migraine for at least one year prior to inclusion, with the onset of episodic migraine occurring before the age of 50 and chronic migraine before the age of 65. The trial population is selected based on their pharmacological refractoriness, defined by insufficient treatment effect, contraindications, or intolerable side effects from at least three medications across two different drug classes. Participants must have maintained stable preventive headache medication regimens for at least three months prior to the study and agree to continue these regimens throughout the trial. The sponsor has not provided information regarding the total number of participants. The study includes a vulnerable population, and participants must master a Scandinavian language to fully understand the study information. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **botulinum toxin type A** in the treatment of **chronic migraine**. This study is a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thus minimizing bias. The trial is set to run from October 1, 2019, to December 31, 2034, with recruitment having started on January 1, 2019. Participants will be involved in the study for a maximum treatment period of one month, with the possibility of early termination if they experience intolerable side effects or fail to comply with study procedures.
The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age, language proficiency, and a history of chronic migraine. Following the screening, participants will undergo baseline assessments before randomization. The primary endpoint is the difference in change from baseline in the mean monthly headache days at weeks 5 to 8 post-intervention between the treatment and placebo groups. Secondary endpoints include the occurrence of adverse events, changes in migraine days, headache intensity, and quality of life.
Participants will attend follow-up visits at specified intervals to monitor treatment effects and any adverse events. The end-of-study visit will conclude the trial for each participant, where final assessments will be conducted. Conditions for early termination include significant protocol deviations or the emergence of contraindications. The trial aims to provide robust data on the effectiveness of botulinum toxin type A in managing chronic migraine, potentially offering a new therapeutic option for patients with treatment-refractory conditions.
Treatment
The clinical trial involves the administration of two treatments. The first treatment is **Natriumklorid B. Braun 9 mg/ml**, a **solution for infusion** containing the active substance **sodium chloride**. This pharmaceutical form is provided as an infusion solution and is administered via **injection**. The maximum daily dose is 0.5 ml, with a total dose not exceeding 0.5 ml per day. The treatment period is limited to one day. Sodium chloride is a chemical substance, and the product is manufactured by B.BRAUN MELSUNGEN AG. This treatment serves as a placebo in the trial.
The second treatment is **BOTOX 100 Allergan-enheter**, a **solution for injection** containing the active substance **botulinum toxin type A**. This product is administered via **injection** with a maximum daily dose of 50 IU and a total dose not exceeding 50 IU per day. The treatment period is also limited to one day. Botulinum toxin type A is a protein-based substance, and the product is manufactured by ABBVIE AS. This treatment is the experimental medication being tested for its efficacy in blocking the sphenopalatine ganglion in patients with treatment-refractory chronic migraine. The trial aims to evaluate the effectiveness of this treatment using an image-guided surgical device, MultiGuide®.
Efficacy
The efficacy of the treatment in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the difference in change from baseline in the mean monthly headache days at weeks 5 to 8 post-intervention between the treatment and placebo groups. This will provide a direct measure of the treatment's impact on headache frequency.
Secondary endpoints include several additional measures to comprehensively evaluate the treatment's efficacy. These include the difference in occurrence of adverse events and serious adverse events between the treatment and placebo groups, the difference in change from baseline in the mean monthly migraine days, and the difference in the number of treatment responders, defined as those with a ≥30% reduction in mean monthly headache days at weeks 5 to 8 post-intervention compared to baseline. Other secondary endpoints involve the difference in change from baseline in the mean monthly headache intensity, the mean monthly occurrence of cumulative hours per 28 days of moderate/severe pain, and the mean monthly number of days with rescue medication. Additionally, a migraine-specific quality of life questionnaire will be utilized to assess the impact of the treatment on patients' quality of life.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Informed and written consent
- Male or female, between 18 and 70 years of age
- Masters a Scandinavian language at level sufficient to fully understand the written and verbal study information
- Migraine, with or without aura, fulfilling the International Classification of Headache Disorders (ICHD) III criteria 1.3. for chronic migraine at time of inclusion
- Chronic migraine at least for a period of 1 year prior to inclusion
- Debut of episodic migraine before the age of 50, and chronic migraine before the age of 65.
- The condition is pharmacologically refractory as defined in this study as insufficient treatment effect, contraindication(s) or intolerable side effect(s) of at least 3 medications from at least 2 of the following medication (drug) classes a. Beta-blockers b. RA(A)S-inhibitors c. Calcium-antagonists d. Antiepileptic drugs e. Tricyclic antidepressants f. Botulinum toxin A g. CGRP antagonists
- 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.
- Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during the whole study period.
- In the case of women of childbearing potential (WOCBP) they have to commit to highly effective contraception in a period of 4 weeks after injection (for details, confer section 4.3)
- Ability to understand study procedures and to comply with them for the entire length of the study
Exclusion Criteria
- Allergy or hypersensitivity reactions to marcaine, lidocaine, xylocaine, adrenaline, any botulinum toxin or similar substances.
- Subject is unable to differentiate migraine from other concomitant headaches.
- Subject with secondary headache conditions, with the exception of medication overuse headache.
- Non-responder in regular clinical practice to preventive medications from ≥6 of the following 7 drug classes: a. Beta-blockers b. RA(A)S-inhibitors c. Calcium-antagonists d. Antiepileptic drugs e. Tricyclic antidepressants f. Botulinum toxin A g. CGRP antagonists
- Subject has had a 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.
- Subject has had a change in type, dosage or dose frequency of preventive headache medications during the baseline period, eg. prior to IMP administration
- Botulinum toxin injections in the head and neck region, as part of migraine treatment or otherwise indicated on medical or cosmetic grounds, in the last 4 months before inclusion.
- The discontinuation of CGRP-antagonists within 3 months before study inclusion or 5 half-lives, whichever is longer.
- Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study inclusion or 5 half-lives, whichever is longer.
- Subject is currently participating or has participated in the last 3 months in another clinical study in which the subject has, is, or will be exposed to an investigational or non-investigational drug or device.
- Subject has had previous radiofrequency ablation, balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the trigeminal ganglion or any branch of the trigeminal nerve.
- Subject has had previous radiofrequency ablation (including non-lesional pulsed radiofrequency), balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the SPG.
- Subject has had blocks of short-acting anaesthetics of the SPG in the last 3 months.
- Subject is or has been treated with occipital nerve stimulation or deep brain stimulation.
- Ongoing abuse of drugs (including narcotics) or alcohol.
- More than 4 days of opioid use per month (including codeine and tramadol), and any use of barbiturates
- Treatment with pharmacological substances prior to SPG-injection that may interact with BTA (aminoglycosides, spectinomycin, neuromuscular blockers, both depolarizing agents (such as succinylcholine) or non-depolarizing (tubocurarine derivates), and anticholinesterases).
- Inadequate contraceptive use. Women of childbearing potential (WOCBP) who do not use highly effective contraception (HEC) or use other medication that may interact and/or otherwise reduce the efficacy of the contraceptiva in use.
- Subject has undergone facial surgery in the area of the pterygopalatine fossa or zygomaticomaxillary at the planned injection site that, in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
- Facial anomaly or trauma which renders the procedure difficult.
- Subject currently has an active oral or dental abscess or a local infection at the site of injection based on present symptoms.
- 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.
- Patients with comorbid psychiatric disorders with psychotic or other symptoms making compliance with the study protocol difficult, at the discretion of the investigator
- 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
- Patients with disorders that severely inhibits lacrimation, at the discretion of the investigator
- Patients with previous ischemic cardiovascular and cerebrovascular disorder with, in the opinion of the investigator, a moderate to high risk of new ischemic episodes.
- Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection.
- Subject has a history of bleeding disorders or coagulopathy, that, in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
- Unable to stop antithrombotic medication e.g. platelet aggregation inhibitors and/or anticoagulation therapy, prior to procedure.
- The patient cannot participate or successfully complete the study, in the opinion of their healthcare provider or the investigator, for any of the following reasons: • mentally or legally incapacitated or unable to give consent for any reason • in custody due to an administrative or a legal decision, under tutelage, or being admitted to a sanatorium or social institution • has any other condition, which, in the opinion of the investigator, makes the patient inappropriate for inclusion in the study
- The patient is a study centre employee who is directly involved in the study or the relative of such an employee.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Norway | Not Recruiting | 01 Jan 2019 | 170 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Natriumklorid B. Braun 9 mg/ml infusjonsvæske, oppløsning | Placebo | INFUSJONSVÆSKE, OPPLØSNING | INJECTION | 0.5 | 1 | PRD563960 |
BOTOX 100 Allergan-enheter Pulver til injeksjonsvæske, oppløsning | Test | PULVER TIL INJEKSJONSVÆSKE, OPPLØSNING | INJECTION | 50 | 1 | PRD9631600 |