Botulinum Toxin A in Frequent and Chronic Tension-type Headache (BACT)

BACT - Botulinum Toxin A in Frequent and Chronic Tension-type Headache With the FollowTheSutures Paradigm. A Double Blind, Randomized, Placebo-controlled Cross-over Trial

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.

Study Overview

• Status: Completed
• Conditions: Tension-Type Headache
• Intervention / Treatment: Drug: Botulinum Toxin Type A in saline water; Drug: Isotone saline water

Detailed Description

BACT studies the efficacy of treatment with botulinum toxin with a follwthestuture injection regime in frequent and chronic tension type headache (TTH). This is be a randomized, placebo-controlled, triple blind, cross-over trial. The primary efficacy variable is the difference in monthly headache days in the active period versus the placebo period. In this study, injections will follow a slightly modified FollowTheSutures injection protocol. Study duration is 36 weeks long. The target population is male and female patients 18 to 75 years of age with TTH, with 10 or more headache days per month.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• Norway
  • Namsos, Norway
    • Namsos Sykehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

Eligible participants must meet all of the inclusion criteria in this study.

• 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.

Exclusion criteria

All candidates meeting any of the exclusion criteria at baseline or visit nr.2 will be excluded from study participation:

• 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).
• Change in type, dosage or dose frequency of preventive headache medication < 1 months prior to inclusion.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botulinum toxin A injections; Botulinum toxin A (Botox)	Drug: Botulinum Toxin Type A in saline water; 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.; Other Names: Botox; Drug: Isotone saline water; 2ml Na Cl (sodium chloride) 0,9% Braun. 0,1ml per injection point in total 20 injections points; Other Names: Sodium chloride solution; NaCl solution
Placebo Comparator: placebo injections; Isotone saline water	Drug: Botulinum Toxin Type A in saline water; 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.; Other Names: Botox; Drug: Isotone saline water; 2ml Na Cl (sodium chloride) 0,9% Braun. 0,1ml per injection point in total 20 injections points; Other Names: Sodium chloride solution; NaCl solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
50% responders (50% reduction in TTH-headache days from baseline) in week 1-4, 5-8 and 9-12	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	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	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	EQ-5D-5L at week 8 and 12 after injection	36 weeks
Patient Global Impression of Improvement (PGI-I)	scale 7-points - (very much better) to 7 (very much worse) 8 and 12 after injection	36 weeks
Average maximum pain intensity in Numeric Rating Scale (NRS from 0 to10) in week 1-4, 5-8 and 9-12	NRS scale: 0 meaning no pain and 10 meaning the worst pain imaginable)	36 weeks
Headache Impact Test (HIT-6)	HIT-6 at week 8 and 12 after injection	36 weeks
Average number of headache hours per day in week 1-4, 5-8 and 9-12.	Average number of headache hours per day in week 1-4, 5-8 and 9-12.	36 weeks
Average number of days with intake of painkillers per month in week 1-4, 5-8 and 9-12	Average number of days with intake of painkillers per month in week 1-4, 5-8 and 9-12	36 weeks
Acceptability	Acceptability	36 weeks
Difference in occurrence of adverse events and serious adverse events in the active period and the placebo period	Difference in occurrence of adverse events and serious adverse events in the active period and the placebo period	36 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
e the efficacy of BoNT in treatment group as compared to placebo group in reducing the area-under-the-headache curve (AUC)	Tertiary/Exploratory objective and endpoints Exploratory objective: To investigate the efficacy of BoNT in treatment group as compared to placebo group in reducing the area-under-the-headache curve (AUC). This variable defined according to IHS-guidelines(22) Exploratory endpoint: To investigate the efficacy of BoNT in treatment group as compared to placebo group in reducing the area-under-the-headache curve (AUC). The area-under-the-headache curve (AUC) is validated and recommended by the International Headache Society for controlled trials of preventive treatment of TTH in adults . The AUC measurement combines headache intensity and headache duration, and it will provide more insights to how the burden of headache has changed after the intervention than the primary efficacy measures (days with TTH). AUC is defined accordingly as the sum of the daily recordings of the headache duration multiplied with the headache intensity (also called headache index).	recorded daily as ePROMs in an eDiary throughout the study participation.

Collaborators and Investigators

• Sponsor: Helse Nord-Trøndelag HF
• Collaborators: Norwegian University of Science and Technology; Sandvika Nevrosenter
• Investigators: Study Director: Norunn Hanssen Hestvik, Clinic for Medicine and rehabilitation, Nord Trøndelag Trust HNT

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Actual): December 4, 2024
• Study Completion (Actual): December 4, 2024

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Injections; Botulinum toxins, type A
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Headache; Tension-Type Headache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Cholinergic Agents; Neuromuscular Agents; Acetylcholine Release Inhibitors; Pharmaceutical Solutions; Botulinum Toxins, Type A; abobotulinumtoxinA; Botulinum Toxins
• Other Study ID Numbers: 90953; 2019-001385-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No