Medication Overuse HeadacheDEFINE3NCT02993289
Is Detoxification Needed in Medication-overuse Headache?
A study testing Different well-known treatments in people with Medication Overuse Headache, run by Danish Headache Center at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Medication Overuse Headache
- What is being tested?
- Different well-known treatments
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 1 siteDenmark
- Study dates
- 24 Oct 2016to 30 Nov 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 23Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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:
- 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.
- Conditions
- Medication Overuse Headache
- Being tested
- Different well-known treatments
- Medical subject headings
- Headache Disorders, Secondary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Different well-known treatmentsOther
| Study group | Role | What they receive |
|---|---|---|
| Detoxification and pharmacological prophylactic treatment | Active comparator | Group A: Two months detoxification program combined with pharmacological prophylactic treatment from start. Receives: Other: Different well-known treatments |
| Pharmacological prophylactic treatment | Active comparator | Pharmacological prophylactic treatment from start without detoxification. Receives: Other: Different well-known treatments |
| Detoxification | Active comparator | Two months detoxification program with postponed pharmacological prophylactic treatment after ended detoxification. Receives: Other: Different well-known treatments |
| Control group 1: Episodic migraine | No intervention | Not described |
| Control group 2: Healthy volunteers | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in headache days per month in group A and C compared to group B.
Measured: Six months follow-up
Secondary outcomes (12)
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).
Measured: Two and 12 months follow-up and 4 years
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).
Measured: 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%).
- 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).
Measured: Two, 6 and 12 months follow-up and 4 years
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).
Measured: Two, 6 and 12 months follow-up and 4 years
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).
Measured: Two, 6 and 12 months follow-up
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).
Measured: Two, 6 and 12 months follow-up
Drop-out rate.
Measured: One, 2, 4, 6, 9 and 12 months follow-up and 4 years
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).
Measured: Six and 12 months follow-up
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).
Measured: Six and 12 months follow-up
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).
Measured: Six and 12 months follow-up
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).
Measured: Twelve months follow-up.
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).
Measured: Two, 6 and 12 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2016 (estimated)
- Study start24 Oct 2016
- Primary completion2 Jul 2019
- Study completion30 Nov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Medication Overuse HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 115 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Danish Headache Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Louise Carlsen, Danish Headache Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02993289
- Sponsor's protocol ID
- H-16029763
- Acronym
- DEFINE3
- Status last verified
- Jun 2020
- First submitted
- 8 Dec 2016
- Last updated
- 11 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Carlsen LN, Hansen CS, Kogelman LJA, Werge TM, Ullum H, Bybjerg-Grauholm J, Hansen TF, Jensen RH. DNA-methylation and immunological response in medication overuse headache. Cephalalgia. 2023 Mar;43(3):3331024221147482. doi: 10.1177/03331024221147482.
PubMed 36786322Carlsen 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.
PubMed 32453406
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is Detoxification Needed in Medication-overuse Headache?: A Randomized Controlled Trial of 3 Treatment Strategies
- ClinicalTrials.gov ID
- NCT02993289
- Acronym / sponsor ID
- DEFINE3 / H-16029763
- Conditions
- Medication Overuse Headache
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 115 participants (estimated)
- Lead sponsor
- Danish Headache CenterUniversity, hospital or other
- Study start
- 24 Oct 2016 (actual)
- Primary completion
- 2 Jul 2019 (actual)
- Study completion
- 30 Nov 2023 (estimated)
- First posted
- 15 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Detoxification and pharmacological prophylactic treatment | Active comparator | Other: Different well-known treatmentsGroup A: Two months detoxification program combined with pharmacological prophylactic treatment from start. |
| Pharmacological prophylactic treatment | Active comparator | Other: Different well-known treatmentsPharmacological prophylactic treatment from start without detoxification. |
| Detoxification | Active comparator | Other: Different well-known treatmentsTwo months detoxification program with postponed pharmacological prophylactic treatment after ended detoxification. |
| Control group 1: Episodic migraine | No intervention | – |
| Control group 2: Healthy volunteers | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Different well-known treatments | Other | Detoxification, Detoxification and pharmacological prophylactic treatment, Pharmacological prophylactic treatment |
Primary outcome
Reduction in headache days per month in group A and C compared to group B.
Time frame: Six months follow-up
12 secondary outcomes
Reduction in headache days per month
Time frame: 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
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
Reduction in headache intensity.
Time frame: 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
Changes in Headache Under-Response to Treatment (HURT)-score.
Time frame: 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
Changes in Hospital Anxiety and Depression Scale (HADS).
Time frame: Six and 12 months follow-up
Changes in Quality of Life (QoL) score.
Time frame: Six and 12 months follow-up
Changes in Severity of Dependence Score (SDS).
Time frame: Six and 12 months follow-up
Changes in Perceived Stress Score (PSS).
Time frame: Twelve months follow-up.
Patient's satisfaction questionnaire
Time frame: Two, 6 and 12 months follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
- Derived from this study: PubMed 36786322Carlsen LN, Hansen CS, Kogelman LJA, Werge TM, Ullum H, Bybjerg-Grauholm J, Hansen TF, Jensen RH. DNA-methylation and immunological response in medication overuse headache. Cephalalgia. 2023 Mar;43(3):3331024221147482. doi: 10.1177/03331024221147482.
- Derived from this study: PubMed 32453406Carlsen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Different well-known treatments in people with Medication Overuse Headache, run by Danish Headache Center at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in headache days per month in group A and C compared to group B. (time frame: Six months follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02993289, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020; AzTrials last refreshed its copy on 28 Oct 2026.