Is Detoxification Needed in Medication-overuse Headache? (DEFINE3)

June 9, 2020 updated by: Louise Carlsen, Danish Headache Center

Is Detoxification Needed in Medication-overuse Headache?: A Randomized Controlled Trial of 3 Treatment Strategies

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

115

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Copenhagen
      • Glostrup, Copenhagen, Denmark, 2600
        • Danish Headache Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Detoxification and pharmacological prophylactic treatment
Group A: Two months detoxification program combined with pharmacological prophylactic treatment from start.
Other: Different well-known treatments
Active Comparator: Pharmacological prophylactic treatment
Pharmacological prophylactic treatment from start without detoxification.
Other: Different well-known treatments
Active Comparator: Detoxification
Two months detoxification program with postponed pharmacological prophylactic treatment after ended detoxification.
Other: Different well-known treatments
No Intervention: Control group 1: Episodic migraine
No Intervention: Control group 2: Healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Reduction in headache days per month in group A and C compared to group B.
Time Frame: Six months follow-up
Six months follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduction in headache days per month
Time Frame: Two and 12 months follow-up and 4 years
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Two and 12 months follow-up and 4 years
Reduction in days/month with use of analgesics and/or migraine medication.
Time Frame: Two, 6 and 12 months follow-up and 4 years
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Two, 6 and 12 months follow-up and 4 years
Responders based on reduction in headache days / month (percentage with more than 30%, 50% and 75%).
Time Frame: Two, 6 and 12 months follow-up and 4 years
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Two, 6 and 12 months follow-up and 4 years
Reduction in headache intensity.
Time Frame: Two, 6 and 12 months follow-up and 4 years
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. 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).
Two, 6 and 12 months follow-up and 4 years
Descriptive report of self-reported adverse effects of treatments.
Time Frame: Two, 6 and 12 months follow-up
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Two, 6 and 12 months follow-up
Changes in Headache Under-Response to Treatment (HURT)-score.
Time Frame: Two, 6 and 12 months follow-up
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Two, 6 and 12 months follow-up
Drop-out rate.
Time Frame: One, 2, 4, 6, 9 and 12 months follow-up and 4 years
One, 2, 4, 6, 9 and 12 months follow-up and 4 years
Changes in Hospital Anxiety and Depression Scale (HADS).
Time Frame: Six and 12 months follow-up
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Six and 12 months follow-up
Changes in Quality of Life (QoL) score.
Time Frame: Six and 12 months follow-up
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Six and 12 months follow-up
Changes in Severity of Dependence Score (SDS).
Time Frame: Six and 12 months follow-up
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Six and 12 months follow-up
Changes in Perceived Stress Score (PSS).
Time Frame: Twelve months follow-up.
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Twelve months follow-up.
Patient's satisfaction questionnaire
Time Frame: Two, 6 and 12 months follow-up
  1. Group A and C versus group B.
  2. Group A (detoxification with prophylaxis) versus group C (detoxification with postponed prophylaxis).
  3. Group B (single-therapy with prophylaxis) versus group C (detoxification with postponed prophylaxis).
Two, 6 and 12 months follow-up

Other Outcome Measures

Outcome Measure
Time Frame
Difference in DNA-profile between patients with MOH and controlgroups.
Time Frame: Baseline
Baseline
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
From baseline to 6 months follow-up
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
At 6 and 12 months follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Danish Headache Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 24, 2016

Primary Completion (Actual)

July 2, 2019

Study Completion (Anticipated)

November 30, 2023

Study Registration Dates

First Submitted

December 8, 2016

First Submitted That Met QC Criteria

December 12, 2016

First Posted (Estimate)

December 15, 2016

Study Record Updates

Last Update Posted (Actual)

June 11, 2020

Last Update Submitted That Met QC Criteria

June 9, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-16029763

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Medication Overuse Headache

Clinical Trials on Different well-known treatments

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Singapore

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe