Safety and Efficacy of Botulinum Toxin A in Patients With Posttraumatic Headache

NCT06839118 | Recruiting Phase 3 DMC

• 1 other identifier: 2024-515901-24-00
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The study is an investigator-initiated randomized, placebo-controlled, double-blind, parallelgroup trial. Eighty subjects with PTH will be included and randomized 1:1 for treatment with BTX-A or placebo (isotonic saline). The study comprises a 4-week baseline phase before injection of either active drug or placebo followed by a 12-week evaluation period. Treatment will be double-blind, and subjects will only receive one treatment cycle. Endpoints will be assessed in the evaluation period (weeks 5 to 8) compared to baseline (weeks -4 to -1).

Conditions

Posttraumatic Headache

Outcome Measures

Primary Outcomes (1)

• Primary aim

  To investigate if botulinum toxin type A (BTX-A) is safe and more effective than placebo to lower the number of moderate-to-severe headache days in the evaluation period (weeks 5 to 8) compared to baseline (weeks -4 to -1). Headache days will defined as mild, moderate or severe in intensity based on the International Headache Society guideline for conduction studies on preventive medication in post-traumatic headache

  3 months

Secondary Outcomes (9)

• First secondary aim

  2 months

• Second secondary aim

  3 months

• Third secondary aim

  3 months

• Fourth secondary aim

  3 months

• Fifth secondary aim

  3 months

Study Arms (2)

BTX-A

EXPERIMENTAL

BTX-A used in this study will be Botox® and delivered in vials. A concentration of 50U/mL BTX-A is prepared using saline in four syringes: one with 1 mL, one with 0.8 mL, one with 0.7 mL, one with 0.6 mL. This equals a total administration dose of 155U.

Drug: Botox 200 UNT Injection

Isotonic saline

PLACEBO COMPARATOR

Placebo syringes are prepared exclusively with similar amounts of fluid as in the BTX-A arm.

Drug: Botox 200 UNT Injection

Interventions

Botox 200 UNT Injection DRUG

A concentration of 50U/mL BTX-A is prepared using saline in four syringes: one with 1 mL, one with 0.8 mL, one with 0.7 mL, one with 0.6 mL. This equals a total administration dose of 155U. A total of 155U BTX-A will be injected at day 1 (first day in week 1) by subcutaneous injections according to the PREEMPT protocol.

Also known as: Botulinumtoxin-A

BTX-A; Isotonic saline

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age between 18 and 80 years.
• Subjects must have headache at least 15 days per month during the last 4 weeks to enter the baseline phase.
• 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).
• Fluency in Danish

You may not qualify if:

• More than 2 TBI's.
• 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.
• 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.
• Ongoing and unstable severe psychiatric disease.
• Anamnestic or clinical symptoms of any kind that are deemed relevant for study participation by the physician who examines the patient.
• A history of migraine or tension-type headache more than 5 days per month before the TBI.
• Medication-overuse headache according to the according to The International Classification of Headache Disorders 3rd edition.
• A history of moderate-to-severe TBI, whiplash injury, or craniotomy.
• 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).
• Previous treatment with injections of BTX-A in the head or face.
• Female subjects either pregnant, breastfeeding or with planned conception within the study period.
• 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:
• Age ≥ 55 years with cessation of menses for 12 or more months, OR
• Age \< 55 years but no spontaneous menses for at least 2 years, OR
• 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.

Sponsors & Collaborators

• Danish Headache Center: lead

Study Sites (1)

Danish Headache Center

Glostrup Municipality, 2600, Denmark

RECRUITING

MeSH Terms

Conditions

Post-Traumatic Headache

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Lucia Zavala, MD

CONTACT

38632062; lucia.jimena.zavala@regionh.dk

Henrik Schytz, MD

CONTACT

38632062; henrik.winther.schytz.01@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 21, 2025
• Study Start: January 10, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)