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

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ClinicalTrials.gov Identifier: NCT02993289
Recruitment Status : Recruiting
First Posted : December 15, 2016
Last Update Posted : December 20, 2016
Sponsor:
Information provided by (Responsible Party):

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:

  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.

Condition or disease Intervention/treatment
Medication Overuse Headache Other: Different well-known treatments

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 115 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Is Detoxification Needed in Medication-overuse Headache?: A Randomized Controlled Trial of 3 Treatment Strategies
Study Start Date : October 2016
Estimated Primary Completion Date : October 2017
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

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


Outcome Measures

Primary Outcome Measures :
  1. Reduction in headache days per month in group A and C compared to group B. [ Time Frame: Six months follow-up ]
  2. Number Needed to Treat based on cured medication-overuse headache in group A and C compared to group B. [ Time Frame: Six months follow-up ]

Secondary Outcome Measures :
  1. Reduction in headache days per month [ Time Frame: Two 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).

  2. Number Needed to Treat based on cured medication-overuse headache [ Time Frame: Two 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).

  3. Reduction in days/month with use of analgesics and/or migraine medication. [ 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).

  4. 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 ]
    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).

  5. Reduction in headache intensity. [ 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).

    This outcome will be presented as 1) Total headache intensity per month, and as 2) Visual Analogue Scale (VAS).


  6. 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).

  7. 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).

  8. Drop-out rate. [ Time Frame: One, 2, 4, 6, 9 and 12 months follow-up ]
  9. 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).

  10. 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).

  11. 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).

  12. 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).

  13. 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).


Other Outcome Measures:
  1. Difference in DNA-profile between patients with MOH and controlgroups. [ Time Frame: Baseline ]
  2. 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 ]
  3. 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 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02993289


Contacts
Contact: Louise Ninett Carlsen, Medical doctor, PhD-student +45 38633553 louise.ninett.carlsen@regionh.dk

Locations
Denmark
Danish Headache Center Recruiting
Glostrup, Copenhagen, Denmark, 2600
Contact: Louise Ninett Carlsen, Phd-student    +4538633553    louise.ninett.carlsen@regionh.dk   
Sponsors and Collaborators
Danish Headache Center
More Information

Responsible Party: Louise Carlsen, Medical doctor, PhD-student, Danish Headache Center
ClinicalTrials.gov Identifier: NCT02993289     History of Changes
Other Study ID Numbers: H-16029763
First Posted: December 15, 2016    Key Record Dates
Last Update Posted: December 20, 2016
Last Verified: December 2016

Additional relevant MeSH terms:
Headache
Headache Disorders, Secondary
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Headache Disorders
Brain Diseases
Central Nervous System Diseases