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

Sponsor

Helse Nord-Trøndelag HF (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04857671

Collaborator

Norwegian University of Science and Technology (Other), Sandvika Nevrosenter (Other)

Enrollment

Location

Arms

29.3

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tension-Type Headache	Drug: Botulinum Toxin Type A in saline water Drug: Isotone saline water	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

The screening/baseline period with headache diary will be 4 weeks long. Then will all participants be randomized into 2 groups for 2 periods in cross over method. They will get two injections during this study: one injection with botulinum toxin (Botox) and one with placebo (NaCl 0,9% Braun). After each in injections there will be a 12 weeks long follow up period, where participants continue to keep a headache diary and register adverse events. Participant will also have a 4 weeks long wash-out period after the first treatment period. A study nurse or researcher will call participants 4 times during the trial to promote headache diary and check for adverse events.The screening/baseline period with headache diary will be 4 weeks long. Then will all participants be randomized into 2 groups for 2 periods in cross over method. They will get two injections during this study: one injection with botulinum toxin (Botox) and one with placebo (NaCl 0,9% Braun). After each in injections there will be a 12 weeks long follow up period, where participants continue to keep a headache diary and register adverse events. Participant will also have a 4 weeks long wash-out period after the first treatment period. A study nurse or researcher will call participants 4 times during the trial to promote headache diary and check for adverse events.

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Botulinum Toxin A in Frequent and Chronic Tension-type Headache: A Double Blind, Randomized, Placebo-controlled Cross-over Trial

Anticipated Study Start Date :

May 23, 2022

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Botulinum toxin A injections Botulinum toxin A (Botox)	Drug: Botulinum Toxin Type A in saline water 150 Allergan units Botulinum toxin A in a total of 3 ml sodium chloride (NaCl) 0,9% Braun. 5 IU of Botox per injection point (0,1ml); in total 150 IU per 30 injections points. Other Names: Botox Drug: Isotone saline water 3ml Na Cl (sodium chloride) 0,9% Braun. 0,1ml per injection point in total 30 injections points Other Names: Sodium chloride solution NaCl solution
Placebo Comparator: placebo injections Isotone saline water	Drug: Botulinum Toxin Type A in saline water 150 Allergan units Botulinum toxin A in a total of 3 ml sodium chloride (NaCl) 0,9% Braun. 5 IU of Botox per injection point (0,1ml); in total 150 IU per 30 injections points. Other Names: Botox Drug: Isotone saline water 3ml Na Cl (sodium chloride) 0,9% Braun. 0,1ml per injection point in total 30 injections points Other Names: Sodium chloride solution NaCl solution

Arm

Intervention/Treatment

Experimental: Botulinum toxin A injections

Botulinum toxin A (Botox)

Drug: Botulinum Toxin Type A in saline water

150 Allergan units Botulinum toxin A in a total of 3 ml sodium chloride (NaCl) 0,9% Braun. 5 IU of Botox per injection point (0,1ml); in total 150 IU per 30 injections points.

Other Names:

Botox

Drug: Isotone saline water

3ml Na Cl (sodium chloride) 0,9% Braun. 0,1ml per injection point in total 30 injections points

Other Names:

Sodium chloride solution

NaCl solution

Placebo Comparator: placebo injections

Isotone saline water

Drug: Botulinum Toxin Type A in saline water

150 Allergan units Botulinum toxin A in a total of 3 ml sodium chloride (NaCl) 0,9% Braun. 5 IU of Botox per injection point (0,1ml); in total 150 IU per 30 injections points.

Other Names:

Botox

Drug: Isotone saline water

3ml Na Cl (sodium chloride) 0,9% Braun. 0,1ml per injection point in total 30 injections points

Other Names:

Sodium chloride solution

NaCl solution

Outcome Measures

Primary Outcome Measures

days with headache per month [12 weeks]
'during the active period'

Secondary Outcome Measures

Maximum pain intensity [36 weeks]
on a 0-10 numerical rating scale (NRS) 'during the active period'
Number of headache hours per day [36 weeks]
'during the active period'
Number of days with intake of pain-killers per month [36 weeks]
'during the active period'
Quality of life score on EQ-5D-5L [36 weeks]
EQ-5D-5L
Patient Global Impression of Improvement (PGI-I) [36 weeks]
scale 7-points - (very much better) to 7 (very much worse)
Mean monthly headache days from baseline [36 weeks]
during the study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

frequent or chronic tension type headache according to ICHD-3 with 10 or more headache days per month
Headache history of minimum one year.
Previously failed treatment with intolerable side-effects to or contra-indications to at least one tension-type headache 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. Such methods 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
Signed informed consent

Exclusion Criteria:

migraine with more than 1 migraine day per month
other forms of primary or secondary headaches; including medication overuse headache (MOH)
Change in type, dosage or dose frequency of preventive headache or sleep medications < 1 months prior to inclusion
Previous exposure at any time to any botulinum toxin serotype
Pregnancy, breastfeeding or planned pregnancy
Inadequate contraceptive use. Women of childbearing potential (WOCBP) who do not use highly effective contraception (HEC) will be excluded
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
currently having an active local infection at the sites of injection based on present symptoms.
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.
Serious psychiatric disease that may affect study in opinion of study investigator
Other severe chronical pain conditions
Ongoing abuse of alcohol or illicit drugs in the opinion of the investigator
Participating in another trial that might affect the current study