Botulinum Toxin A in Frequent and Chronic Tension-type Headache

NCT04857671 | Completed Phase 3 DMC

• 2 other identifiers: 909532019-001385-16
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic tension-type headache (CTTH) is an underestimated disabling condition that affects a large number of patients. The treatment options for both episodic tension-type headaches, but especially CTTH are few. Poor long-term effects of existing treatment for CTTH (Sarotex, SSRIs, physiotherapy) are reported. Patients with CTTH also have a high risk of developing drug overdose headache (MOH). Non-drug treatments with physiotherapy or alternative medicine also show poor long-term effects. Literature reviews show that there is surprisingly little research on CTTH. Some small clinical trials report a good effect of treatment with botulinum toxin A, but larger controlled trials are needed to confirm or deny this. The investigators will study effect of treatment with botulinum toxin A in CTTH in BACT study, and will include participants with both frequent and chronic TTH with 10 or more headache days per month. If BACT outcomes are positive, this will open a possibility for a new treatment for TTH patients.

Conditions

Tension-Type Headache

Keywords

Botulinum toxins, type A; Injections

Outcome Measures

Primary Outcomes (1)

• Difference in TTH-headache days in week 5-8 of the active period versus the placebo period.

  Difference in TTH- headache days in week 5-8 of the active period versus the placebo period.

  36 weeks

Secondary Outcomes (11)

• 50% responders (50% reduction in TTH-headache days from baseline) in week 1-4, 5-8 and 9-12

  36 weeks

• Difference in TTH-headache days in week 1-4 and 9-12, and in the entire treatment period

  36 weeks

• 30% responders (30% reduction in TTH-headache days from baseline) in week 1-4, 5-8 and 9-12

  36 weeks

• Quality of life score on EQ-5D-5L

  36 weeks

• Patient Global Impression of Improvement (PGI-I)

  36 weeks

Other Outcomes (1)

• e the efficacy of BoNT in treatment group as compared to placebo group in reducing the area-under-the-headache curve (AUC)

  recorded daily as ePROMs in an eDiary throughout the study participation.

Study Arms (2)

Botulinum toxin A injections

EXPERIMENTAL

Botulinum toxin A (Botox)

Drug: Botulinum Toxin Type A in saline water; Drug: Isotone saline water

placebo injections

PLACEBO COMPARATOR

Isotone saline water

Drug: Botulinum Toxin Type A in saline water; Drug: Isotone saline water

Interventions

Botulinum Toxin Type A in saline water DRUG

100 Allergan units Botulinum toxin A in a total of 2 ml sodium chloride (NaCl) 0,9% Braun. 5 IU of Botox per injection point (0,1ml); in total 100 IU per 20 injections points.

Also known as: Botox

Botulinum toxin A injections; placebo injections

Isotone saline water DRUG

2ml Na Cl (sodium chloride) 0,9% Braun. 0,1ml per injection point in total 20 injections points

Also known as: Sodium chloride solution, NaCl solution

Botulinum toxin A injections; placebo injections

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years
• Frequent or chronical tension type headache according to the ICHD-3 (2.2.3) criteria with 10 or more headache days per month
• Headache history of minimum one year.
• Previously unsatisfactory treatment effect, bothersome side-effects to or contra-indications to at least one TTH prophylactic drug.
• Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during the whole study period.
• In case of women of childbearing potential (WOCBP) they have to be using highly effective contraception (for more details below).
• Signed informed consent.

You may not qualify if:

• Patients with migraine with more than 1 migraine day per month.
• Patients with other forms of primary or secondary headaches; including medication overuse headache (MOH).
• Previous exposure at any time to any botulinum toxin serotype.
• Pregnancy, breastfeeding or planned pregnancy.
• Patients with diseases that are contraindications for use of BoNT-A (Myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, other diseases interfering with neuromuscular function) or allergy to BoNT-A, or treatment with drugs affecting the neuromuscular junction;
• Active infection at the sites of injection
• 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.
• Any psychiatric disorder that may affect ability to comply with study procedures in the opinion of study investigator.
• Other severe chronical pain conditions.
• Abuse of alcohol or illicit drugs.
• Participating in another trial that might affect the current study.
• Contraception for women of childbearing potential (WOCBP) Such methods will include combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence. This group of patients should not be using other drugs that might interact and reduce the efficacy of the used anticonceptive drug. WOCBP is defined as fertile women, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods, include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
• Ability to understand study procedures and to comply with them for the entire length of the study. WOCBP will have to agree to take a pregnancy test before the injection with the study drug.

Sponsors & Collaborators

• Helse Nord-Trøndelag HF: lead
• Norwegian University of Science and Technology: collaborator
• Sandvika Nevrosenter: collaborator

Study Sites (1)

Namsos Sykehus

Namsos, Norway

Location

MeSH Terms

Conditions

Tension-Type Headache

Interventions

Botulinum Toxins, Type A; Saline Waters; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Norunn Hanssen Hestvik

  Clinic for Medicine and rehabilitation, Nord Trøndelag Trust HNT

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In this study, injections will follow a slightly modified FollowTheSutures injection protocol. Study duration is 36 weeks long. A 4 weeks screening/baseline period with a daily electronic headache diary (eDiary) follows inclusion and informed consent. After completing the 4-week screening/baseline period, participants will be re-screened and eligible participants will enter the randomized phase of the study consisting of two treatment periods. The treatment periods is either injections with verum (onabotulinum toxin suspended in saline (Botox® and NaCl 0,9% Braun) or placebo (only NaCl 0,9% Braun). The participants are randomized to the order with which they enter the two periods, and a quadruple-blinding regime is implemented. Each treatment period lasts 12 weeks, separated by a 4 week washout period. Participants continue to keep a daily eDiary and register adverse events in the entire randomized period.

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: April 23, 2021
• Study Start: October 3, 2022
• Primary Completion: December 4, 2024
• Study Completion: December 4, 2024
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)