Back to resultsIs Detoxification Needed in Medication-overuse Headache? (DEFINE3)
Primary Purpose
Medication Overuse Headache
Status
Active
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Different well-known treatments
Sponsored by
About this trial
This is an interventional treatment trial for Medication Overuse Headache
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.
Sites / Locations
- Danish Headache Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Active Comparator
Active Comparator
Active Comparator
No Intervention
No Intervention
Arm Label
Detoxification and pharmacological prophylactic treatment
Pharmacological prophylactic treatment
Detoxification
Control group 1: Episodic migraine
Control group 2: Healthy volunteers
Arm Description
Group A: Two months detoxification program combined with pharmacological prophylactic treatment from start.
Pharmacological prophylactic treatment from start without detoxification.
Two months detoxification program with postponed pharmacological prophylactic treatment after ended detoxification.
Outcomes
Primary Outcome Measures
Reduction in headache days per month in group A and C compared to group B.
Secondary Outcome Measures
Reduction in headache days per month
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Reduction in days/month with use of analgesics and/or migraine medication.
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Responders based on reduction in headache days / month (percentage with more than 30%, 50% and 75%).
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Reduction in headache intensity.
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
This outcome will be presented as 1) Total headache intensity per month, and as 2) Visual Analogue Scale (VAS).
Descriptive report of self-reported adverse effects of treatments.
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Changes in Headache Under-Response to Treatment (HURT)-score.
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Drop-out rate.
Changes in Hospital Anxiety and Depression Scale (HADS).
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Changes in Quality of Life (QoL) score.
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Changes in Severity of Dependence Score (SDS).
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Changes in Perceived Stress Score (PSS).
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Patient's satisfaction questionnaire
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02993289
Brief Title
Is Detoxification Needed in Medication-overuse Headache?
Acronym
DEFINE3
Official Title
Is Detoxification Needed in Medication-overuse Headache?: A Randomized Controlled Trial of 3 Treatment Strategies
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 24, 2016 (Actual)
Primary Completion Date
July 2, 2019 (Actual)
Study Completion Date
November 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Danish Headache Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
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:
To compare three different treatment protocols in order to improve the therapy of MOH.
To test several baseline variables for being potential predictors for good treatment outcome.
To examine the role of epigenetics in MOH.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medication Overuse Headache
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
115 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Detoxification and pharmacological prophylactic treatment
Arm Type
Active Comparator
Arm Description
Group A: Two months detoxification program combined with pharmacological prophylactic treatment from start.
Arm Title
Pharmacological prophylactic treatment
Arm Type
Active Comparator
Arm Description
Pharmacological prophylactic treatment from start without detoxification.
Arm Title
Detoxification
Arm Type
Active Comparator
Arm Description
Two months detoxification program with postponed pharmacological prophylactic treatment after ended detoxification.
Arm Title
Control group 1: Episodic migraine
Arm Type
No Intervention
Arm Title
Control group 2: Healthy volunteers
Arm Type
No Intervention
Intervention Type
Other
Intervention Name(s)
Different well-known treatments
Primary Outcome Measure Information:
Title
Reduction in headache days per month in group A and C compared to group B.
Time Frame
Six months follow-up
Secondary Outcome Measure Information:
Title
Reduction in headache days per month
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Two and 12 months follow-up and 4 years
Title
Reduction in days/month with use of analgesics and/or migraine medication.
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Two, 6 and 12 months follow-up and 4 years
Title
Responders based on reduction in headache days / month (percentage with more than 30%, 50% and 75%).
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Two, 6 and 12 months follow-up and 4 years
Title
Reduction in headache intensity.
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
This outcome will be presented as 1) Total headache intensity per month, and as 2) Visual Analogue Scale (VAS).
Time Frame
Two, 6 and 12 months follow-up and 4 years
Title
Descriptive report of self-reported adverse effects of treatments.
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Two, 6 and 12 months follow-up
Title
Changes in Headache Under-Response to Treatment (HURT)-score.
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Two, 6 and 12 months follow-up
Title
Drop-out rate.
Time Frame
One, 2, 4, 6, 9 and 12 months follow-up and 4 years
Title
Changes in Hospital Anxiety and Depression Scale (HADS).
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Six and 12 months follow-up
Title
Changes in Quality of Life (QoL) score.
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Six and 12 months follow-up
Title
Changes in Severity of Dependence Score (SDS).
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Six and 12 months follow-up
Title
Changes in Perceived Stress Score (PSS).
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Twelve months follow-up.
Title
Patient's satisfaction questionnaire
Description
Group A and C versus group B.
Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Time Frame
Two, 6 and 12 months follow-up
Other Pre-specified Outcome Measures:
Title
Difference in DNA-profile between patients with MOH and controlgroups.
Time Frame
Baseline
Title
Difference in methylation levels and RNA sequence analysis in patients with MOH undergoing treatment compared to controls.
Time Frame
From baseline to 6 months follow-up
Title
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.
Time Frame
At 6 and 12 months follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Facility Information:
Facility Name
Danish Headache Center
City
Glostrup
State/Province
Copenhagen
ZIP/Postal Code
2600
Country
Denmark
12. IPD Sharing Statement
Citations:
PubMed Identifier
32453406
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.
Results Reference
derived
Learn more about this trial
Is Detoxification Needed in Medication-overuse Headache?
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