Tension-Type Headache
Conditions
Keywords
Botulinum toxins, type A, Injections
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.
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.
Interventions
DRUGBotulinum 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.
DRUGIsotone saline water
2ml Na Cl (sodium chloride) 0,9% Braun. 0,1ml per injection point in total 20 injections points
Sponsors
Norwegian University of Science and Technology
Sandvika Nevrosenter
Helse Nord-Trøndelag HF
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in TTH-headache days in week 5-8 of the active period versus the placebo period. | 36 weeks | Difference in TTH- headache days in week 5-8 of the active period versus the placebo period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 50% responders (50% reduction in TTH-headache days from baseline) in week 1-4, 5-8 and 9-12 | 36 weeks | 50% responders (50% reduction in TTH-headache days from baseline) in week 1-4, 5-8 and 9-12 |
| Difference in TTH-headache days in week 1-4 and 9-12, and in the entire treatment period | 36 weeks | Difference in TTH-headache days in week 1-4 and 9-12, and in the entire treatment period |
| 30% responders (30% reduction in TTH-headache days from baseline) in week 1-4, 5-8 and 9-12 | 36 weeks | 30% responders (30% reduction in TTH-headache days from baseline) in week 1-4, 5-8 and 9-12 |
| Quality of life score on EQ-5D-5L | 36 weeks | EQ-5D-5L at week 8 and 12 after injection |
| Patient Global Impression of Improvement (PGI-I) | 36 weeks | scale 7-points - (very much better) to 7 (very much worse) 8 and 12 after injection |
| Headache Impact Test (HIT-6) | 36 weeks | HIT-6 at week 8 and 12 after injection |
| Average number of headache hours per day in week 1-4, 5-8 and 9-12. | 36 weeks | Average number of headache hours per day 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 | Average number of days with intake of painkillers per month in week 1-4, 5-8 and 9-12 |
| Acceptability | 36 weeks | Acceptability |
| Difference in occurrence of adverse events and serious adverse events in the active period and the placebo period | 36 weeks | Difference in occurrence of adverse events and serious adverse events in the active period and the placebo period |
| Average maximum pain intensity in Numeric Rating Scale (NRS from 0 to10) in week 1-4, 5-8 and 9-12 | 36 weeks | NRS scale: 0 meaning no pain and 10 meaning the worst pain imaginable) |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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). |
Countries
Norway
Outcome results
None listed