Botulinum toxin for Persistent post-traumatic headache|Post-traumatic headache

Inclusion criteria

• {"criterion_text":"- 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.\n- Age between 18 and 80 years.\n- Subjects must have headache at least 15 days per month during the last 4 weeks to enter the baseline phase.\n- 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).\n- Fluency in Danish."}

Exclusion criteria

• {"criterion_text":"- More than two incidences of traumatic brain injuries.\n- Previous treatment with injections of BTX-A in the head or face.\n- Female subjects either pregnant, breastfeeding or with planned conception within the study period.\n- 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).\n- Known allergy to any component of BTX-A.\n- Infection at the proposed injection site.\n- Known severe neuromuscular disorders or any degree of disorder affecting the neuromuscular transmission.\n- Known comprised respiratory function.\n- Member of investigational site staff or relative of the investigator.\n- 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.\n- 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.\n- Ongoing and unstable severe psychiatric disease.\n- Anamnestic or clinical symptoms of any kind that are deemed relevant for study participation by the physician who examines the patient.\n- A history of migraine or tension-type headache more than 5 days per month before the TBI.\n- Medication-overuse headache according to the according to The International Classification of Headache Disorders 3rd edition.\n- A history of moderate-to-severe TBI, whiplash injury, or craniotomy.\n- Change of preventive PTH treatment or treatment dose within two months prior to the baseline visit (see protocol Section 6.4 for a full list of these medications)."}

Primary endpoints

• {"endpoint_text":"- The proportion of responders in BTX-A and placebo group during the evaluation period (weeks 5 to 8) compared with baseline (weeks -4 to -1). A subject who meets the following criterion will be classified as a responder: Has a reduction of ≥ 30% in number of days having moderate or severe headache","definition_or_measurement_approach":"Responder defined as ≥ 30% reduction in number of days with moderate or severe headache during evaluation period (weeks 5 to 8) versus baseline (weeks -4 to -1). Proportion of responders compared between BTX-A and placebo groups."}

Secondary endpoints

• {"endpoint_text":"- The degree of change in inflammatory biomarkers (See protocol Section 7.2.14 for the full list) in plasma and tears in responders versus non-responders in BTX-A and placebo group.","definition_or_measurement_approach":"Change in specified inflammatory biomarkers in plasma and tears; protocol Section 7.2.14 lists full biomarker panel; comparison between responders and non-responders in both treatment arms."}
• {"endpoint_text":"- The proportion of responders in BTX-A and placebo group during the evaluation period (weeks 9 to 12) compared with baseline (weeks -4 to -1). proportion of subjects reaching ≥50% reduction in number of days with moderate-to-severe headache during the evaluation period (weeks 5 to 8) compared with baseline (weeks -4 to -1).","definition_or_measurement_approach":"Proportion of responders during weeks 9–12 vs baseline; also proportion reaching ≥50% reduction in moderate-to-severe headache days during weeks 5–8 vs baseline."}
• {"endpoint_text":"- The proportion of subjects reaching ≥50% reduction in number of days with moderate-to-severe headache during the evaluation period (weeks 5 to 8) compared with baseline (weeks -4 to -1).","definition_or_measurement_approach":"Proportion of subjects with ≥50% reduction in moderate-to-severe headache days during weeks 5–8 vs baseline."}
• {"endpoint_text":"- The proportion of subjects reaching ≥75% reduction in number of days with moderate-to-severe headache during the evaluation period (weeks 5 to 8) compared with baseline (weeks -4 to -1).","definition_or_measurement_approach":"Proportion of subjects with ≥75% reduction in moderate-to-severe headache days during weeks 5–8 vs baseline."}
• {"endpoint_text":"- Proportion of subjects with a PGI-C scale response of “much improved” or “very much improved” at week 8 in BTX-A group and placebo group.","definition_or_measurement_approach":"Patient Global Impression of Change (PGI-C) responses at week 8; proportion reporting 'much improved' or 'very much improved' compared between groups."}
• {"endpoint_text":"- Change from baseline to week 5 in the HIT-6, RPQ, HADS & ISI score in BTX-A and placebo group.","definition_or_measurement_approach":"Change in patient-reported outcome measures (HIT-6, RPQ, HADS, ISI) from baseline to week 5 compared between treatment groups."}
• {"endpoint_text":"- Proportion of dropouts caused by increased intake of PTH medication or use of prohibited rescue medication in BTX-A group compared to the placebo group.","definition_or_measurement_approach":"Proportion of participants who drop out due to increased PTH medication intake or prohibited rescue medication use, compared between groups."}
• {"endpoint_text":"- Proportion of subjects with side effects registered in weeks 2 to 5 during treatment with BTX-A compared with placebo.","definition_or_measurement_approach":"Proportion of subjects with adverse events recorded in weeks 2–5 during treatment compared between BTX-A and placebo."}

Methods

• Doctor-to-doctor invitation letters (Denmark) (document: PTH_BTX-A_Recruitment_Dr_to_Dr_letter).
• Patient association outreach and advertisements targeted to Hjernerystelsesforeningen (Denmark) (documents: PTH_BTX-A_Recruitment_SoMe_Hjernerystelsesforeningen; PTH_BTX-A_Recruitment_Advertisement_Hjernerystelsesforeningen).
• Social media (SoMe) posts and web/poster advertisements (Denmark) (documents: PTH_BTX-A_Recruitment_SoMe_Hjernerystelsesforeningen; PTH_BTX-A_Recruitment_Poster_Web_Post).
• Posters and web posts for public recruitment (Denmark) (document: PTH_BTX-A_Recruitment_Poster_Web_Post).

Denmark

Earliest CTIS Part Ii Submission Date

09-09-2024

Latest Decision Or Authorization Date

03-10-2024

Processing Time Days

24

Number Of Sites

1

Number Of Participants

80

Primary sponsor

Full Name

Rigshospitalet

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"sponsorDuties code 1","organisation_type":"Hospital/Clinic/Other health care facility"}