Using Botox to treat posttraumatic headaches

Safety and Efficacy of Botulinum Toxin A in Patients With Posttraumatic Headache: a Double-blind, Randomized, Placebo-controlled, Parallel-group Trial and Investigation of Neuroinflammatory Biomarkers as Predictors of Efficacy

This study is testing if Botox can help people with posttraumatic headaches feel better by reducing how often and how badly they hurt.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Danish Headache Center (other)
• Locations: 1 site (Glostrup Municipality)
• Trial ID: NCT06839118 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of botulinum toxin type A (BTX-A) in patients suffering from posttraumatic headache (PTH). It is a randomized, placebo-controlled, double-blind trial involving 80 subjects who will be assigned to receive either BTX-A or a placebo after a 4-week baseline phase. The evaluation period lasts for 12 weeks, during which the effectiveness of the treatment will be assessed based on headache frequency and severity. The study aims to explore the potential overlap between PTH and migraine mechanisms, particularly focusing on the role of calcitonin gene-related peptide (CGRP).

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 80 with a diagnosis of persistent posttraumatic headache occurring at least 15 days per month.

Not a fit: Patients with a history of more than two traumatic brain injuries or severe cardiovascular conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the frequency and severity of headaches in patients with posttraumatic headache.

How similar studies have performed: Previous studies have shown promising results with botulinum toxin in treating chronic headaches, suggesting potential success for this approach in posttraumatic headache.

Eligibility criteria

Inclusion Criteria:

1. A diagnosis of persistent PTH according to criteria 5.2.2 Persistent headache attributed to mild traumatic injury to the head according to The International Classification of Headache Disorders 3rd edition.
2. Age between 18 and 80 years.
3. Subjects must have headache at least 15 days per month during the last 4 weeks to enter the baseline phase.
4. During baseline phase subjects must experience moderate-to-severe headache at least 8 days and headache at least 15 days to enter the treatment phase (to be randomized).
5. Fluency in Danish

Exclusion Criteria:

1. More than 2 TBI's.
2. Severe cardiovascular and cerebrovascular disease such as ischemic heart disease, myocardial infarction or previous stroke or transient ischemic attack, major CVD interventions during the last three months.
3. Expected poor compliance, i.e., considered unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge.
4. Ongoing and unstable severe psychiatric disease.
5. Anamnestic or clinical symptoms of any kind that are deemed relevant for study participation by the physician who examines the patient.
6. A history of migraine or tension-type headache more than 5 days per month before the TBI.
7. Medication-overuse headache according to the according to The International Classification of Headache Disorders 3rd edition.
8. A history of moderate-to-severe TBI, whiplash injury, or craniotomy.
9. Change of preventive PTH treatment or treatment dose within two months prior to the baseline visit (see Section 6.4 for a full list of these medications).
10. Previous treatment with injections of BTX-A in the head or face.
11. Female subjects either pregnant, breastfeeding or with planned conception within the study period.
12. Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during the study. Acceptable methods of effective birth control include not having intercourse (true abstinence, when this is in line with the preferred and usual lifestyle of the subject), hormonal birth control methods (pills, shots/injections, implants, or patches), intrauterine devices, surgical contraceptive methods (vasectomy with medical assessment of the surgical success of this procedure or bilateral tubal ligation). Female subjects not of childbearing potential are defined as any female who: is post-menopausal by history, defined as:

    1. Age ≥ 55 years with cessation of menses for 12 or more months, OR
    2. Age \< 55 years but no spontaneous menses for at least 2 years, OR
    3. Age \< 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous, or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels \> 40 IU/L) or postmenopausal estradiol levels (\< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved OR underwent bilateral oophorectomy OR underwent hysterectomy OR underwent bilateral salpingectomy.
13. Known allergy to any component of BTX-A.
14. Infection at the proposed injection site.
15. Known severe neuromuscular disorders or any degree of disorder affecting the neuromuscular transmission.
16. Known comprised respiratory function.
17. Member of investigational site staff or relative of the investigator.

Where this trial is running

Glostrup Municipality

• Danish Headache Center — Glostrup Municipality, Denmark (RECRUITING)

Study contacts

• Study coordinator: Lucia Zavala, MD

Conditions: Posttraumatic Headache