Clinical trial NCT02993289: Is Detoxification Needed in Medication-overuse Headache?
Official title: Is Detoxification Needed in Medication-overuse Headache?: A Randomized Controlled Trial of 3 Treatment Strategies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Medication Overuse Headache
Lead sponsor: Danish Headache Center
Sponsor class: OTHER
First posted: 2016-12-15
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Medication-overuse headache (MOH) is a disabling condition, yet treatable. According to European guidelines and based on evidence, multidisciplinary detoxification is the first choice of treatment for MOH. However, consensus about the details in such detoxification programs is lacking. Contrary, other headache specialists believe more in treating chronic headache with medication overuse with single-therapy of prophylaxis and no withdrawal of acute medication, based on randomized controlled double-blinded placebo trial with prophylaxes. Only a single RCT has compared single-therapy with prophylaxis to detoxification. However there was no significant difference.

AIM:

1. To compare three different treatment protocols in order to improve the therapy of MOH.
2. To test several baseline variables for being potential predictors for good treatment outcome.
3. To examine the role of epigenetics in MOH.


Eligibility criteria: Patients with medication-overuse headache:

Inclusion Criteria:

* Confirmed MOH diagnosis according to the ICHD-III beta (1).
* Eligible for outpatient treatment based on type of medication overuse (without massive pure opioids and barbiturates overuse), and personal resources and motivation.
* Capable of completing headache diary/calendar.
* Age ≥ 18 years old and capable of providing informed consent.
* Medication-overuse headache based on initial tension-type headache (TTH) or migraine.
* Signed informed consent.

Exclusion Criteria:

* Severe physical illness or psychiatric disorders.
* Addiction to alcohol or other drugs.
* Current treatment with headache prophylaxis. Patients can be included minimum 5 weeks after stop of prophylaxis.
* Pregnancy, breastfeeding or planned pregnancy within the next 12 months.
* Inability to provide reliable information about medical history.

Criteria for Control group 1 - Episodic migraineurs:

* Episodic migraine, with/without concomitant tension-type headache, according to the ICHD-III beta.
* Headache days / month ≤ 6 at time of inclusion.
* Days with analgesics / month ≤ 6 at time of inclusion.
* Prophylactics are allowed.
* Age ≥ 18 years old.
* Ability to fill out headache calendar.
* No previous medication overuse.
* No significant co-morbid pain, physical or psychiatric disorders.
* No addiction to alcohol or drug-abuse.
* No pregnancy, breastfeeding or planned pregnancy within the next 12 months.

Criteria for Control group 2 - Healthy volunteers:

•≥ 2 days with headache in the past month at time of inclusion.

* Days with analgesics / month ≤ 6 at time of inclusion.
* Age ≥ 18 years old.
* No significant co-morbid pain, physical or psychiatric disorders.
* No addiction to alcohol or drug-abuse.
* No pregnancy, breastfeeding or planned pregnancy within the next 12 months.

Primary outcomes:
measure: Reduction in headache days per month in group A and C compared to group B.
timeFrame: Six months follow-up
Secondary outcomes:
measure: Reduction in headache days per month
timeFrame: Two and 12 months follow-up and 4 years
measure: Reduction in days/month with use of analgesics and/or migraine medication.
timeFrame: Two, 6 and 12 months follow-up and 4 years
measure: Responders based on reduction in headache days / month (percentage with more than 30%, 50% and 75%).
timeFrame: Two, 6 and 12 months follow-up and 4 years
measure: Reduction in headache intensity.
timeFrame: Two, 6 and 12 months follow-up and 4 years
measure: Descriptive report of self-reported adverse effects of treatments.
timeFrame: Two, 6 and 12 months follow-up
measure: Changes in Headache Under-Response to Treatment (HURT)-score.
timeFrame: Two, 6 and 12 months follow-up
measure: Drop-out rate.
timeFrame: One, 2, 4, 6, 9 and 12 months follow-up and 4 years
measure: Changes in Hospital Anxiety and Depression Scale (HADS).
timeFrame: Six and 12 months follow-up
measure: Changes in Quality of Life (QoL) score.
timeFrame: Six and 12 months follow-up
measure: Changes in Severity of Dependence Score (SDS).
timeFrame: Six and 12 months follow-up
measure: Changes in Perceived Stress Score (PSS).
timeFrame: Twelve months follow-up.
measure: Patient's satisfaction questionnaire
timeFrame: Two, 6 and 12 months follow-up
Other outcomes:
measure: Difference in DNA-profile between patients with MOH and controlgroups.
timeFrame: Baseline
measure: Difference in methylation levels and RNA sequence analysis in patients with MOH undergoing treatment compared to controls.
timeFrame: From baseline to 6 months follow-up
measure: Analysis of association between methylation levels and treatment outcome defined as 1) reduction in headache days per month at 6 months and 12 months and 2) percent of cured vs. percent of relapsers after 12 months.
timeFrame: At 6 and 12 months follow-up
Locations:
city: Glostrup
country: Denmark
facility: Danish Headache Center
state: Copenhagen
Study officials:
References:
citation: Carlsen LN, Munksgaard SB, Nielsen M, Engelstoft IMS, Westergaard ML, Bendtsen L, Jensen RH. Comparison of 3 Treatment Strategies for Medication Overuse Headache: A Randomized Clinical Trial. JAMA Neurol. 2020 Sep 1;77(9):1069-1078. doi: 10.1001/jamaneurol.2020.1179.