Clinical trial NCT02903329: Comparison of Two Detoxification Protocols for Treatment of Medication-overuse Headache
Official title: Efficacy of Restricted Acute Medication Intake Compared to no Acute Medication Intake During a Two Months Detoxification Period in Medication-overuse Headache
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Medication-overuse Headache
Lead sponsor: Danish Headache Center
Sponsor class: OTHER
First posted: 2016-09-16
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Medication-overuse headache (MOH) is a common, costly and disabling disorder affecting approximately 63 million people worldwide. MOH is a potentially treatable condition, and there are different opinions among headache specialists concerning the correct treatment strategy.

The study is a prospective longitudinal open-label randomized controlled study comparing two detoxification programs conducted in a tertiary headache care center. Patients with MOH are either randomized to treatment in program A or program B. In program A, patients undergo detoxification without any acute medication during a two months period (complete stop of acute medication intake). In program B, patients was allowed to take up to 2 days a week with analgesics or migraine medication during the two months detoxification period (restricted acute medication intake). Both A and B are out-patient programs, and patients in both groups receive patient education, consisting of six lessons, managed by specialized headache nurses in collaboration with specialized psychologists and physiotherapists (Figure 1). All patients are also offered rescue medication (levomepromazine or promethazine) and antiemetics, if necessary.

The need for prophylactic treatment is evaluated individually after 2-month detoxification. Patients are followed-up at 2, 6 and 12 months after detoxification. All patients are asked to continuously register headache calendar and to fulfill questionnaires at all the follow-up visits. In addition they are asked to fill out questionnaires (Headache Under-Response to Treatment (HURT), Hospital Anxiety and Depression Score (HADS), Severity of Dependence Score (SDS), World Health Organization Quality of Life Score(WHO QoL) and Dolo-score) at baseline, 2, 6 and 12 months

Detailed description: Patients with contact to Danish headache center are recruited consecutively. The MOH-diagnosis is based on least 3 months previous detailed history and at least 1 month fulfilled headache diary or headache calendar prior to the visit.

Patients were allocated to either program A or B by a concealed randomization process. The patients were randomized in blocks of 10 by use of opaque, sealed envelopes.

Statistics Statistical Package for Social Sciences (SPSS) version 22 is used for statistical calculations. Continuous variables are presented as mean (SD) and median (25-75 percentiles). For normal distributed continuous variables the investigators use paired and unpaired student's T-test, while for skewed distribution the investigators used Mann-Whitney test. Categorical variables is presented as percentage (N), and analyzed by chi-square test. All results are shown as intention-to-treat (ITT). The p-value is two-sided and p ≤ 0.05 is considered as significant.

The primary outcome is reduction in headache days per month. Clinical relevant difference is estimated to 20% between the two groups. The standard deviation based on previous published literature was estimated to 35%. Accepting an alfa-error on 5% and 80% power, 80 patients are needed. Based on previous studies, it is assumed that the drop-out rate will be approximately 15-20%. Therefore the investigators aim to include 100 patients corresponding to 50 in each group.

Eligibility criteria: Inclusion Criteria:

* MOH-diagnosis according to ICHD-3beta
* Eligible for out-patient care
* Previously diagnosed with primary headache forms.

Exclusion Criteria:

* Previously diagnosed with secondary headache forms
* Significant physical or psychiatric illness
* Pregnancy or breastfeeding
* Inadequate language skills to follow the patient education and filling out questionnaires.

Primary outcomes:
measure: Headache frequency
timeFrame: 6 months
Secondary outcomes:
measure: Days with acute medication/ month
timeFrame: 6 and 12 month
measure: Headache frequency
timeFrame: 12 months
measure: Headache intensity (Total intensity per month meassured by headache calendars).
timeFrame: 6 and 12 months
measure: Scores from questionnaires Headache Under-Response to Treatment (HURT)
timeFrame: 6 and 12 months
measure: Scores from questionnaires Hospital Anxiety and Depression Score (HADS)
timeFrame: 6 and 12 months
measure: Scores from questionnaires World Health Organization Quality of Life score
timeFrame: 6 and 12 months
measure: Scores from questionnaires Severity of Dependence Score (SDS)
timeFrame: 6 and 12 months
measure: Scores from questionnaires Dolo-score
timeFrame: 6 and 12 months
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Danish Headache Center
state: Copenhagen
Study officials:
affiliation: Danich Headache Center, Neurological department, Rigshospitalet-Glostrup
name: Louise Ninett Carlsen, MD
role: STUDY_CHAIR
References:
citation: Nielsen M, Carlsen LN, Munksgaard SB, Engelstoft IMS, Jensen RH, Bendtsen L. Complete withdrawal is the most effective approach to reduce disability in patients with medication-overuse headache: A randomized controlled open-label trial. Cephalalgia. 2019 Jun;39(7):863-872. doi: 10.1177/0333102419828994. Epub 2019 Feb 7.
citation: Carlsen LN, Munksgaard SB, Jensen RH, Bendtsen L. Complete detoxification is the most effective treatment of medication-overuse headache: A randomized controlled open-label trial. Cephalalgia. 2018 Feb;38(2):225-236. doi: 10.1177/0333102417737779. Epub 2017 Oct 19.