<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04410536</url>
  </required_header>
  <id_info>
    <org_study_id>MOH</org_study_id>
    <nct_id>NCT04410536</nct_id>
  </id_info>
  <brief_title>Home Detox in Medication Overuse Headache (MOH) During Covid-19 Emergency</brief_title>
  <acronym>MOHC</acronym>
  <official_title>Home-withdrawal Program Combined With Behavioural Approach in Patients With Medication Overuse Headache During Covid-19 Emergency: Incidence of Relapses in Overuse and Changes in Impact at One Year Follow up</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Medication Overuse Headache (MOH) is a disabling condition that affects the 2% of migraine&#xD;
      population. Medication overuse (MO) makes this condition very difficult to treat. The&#xD;
      literature of the last decades confirm the efficacy of withdrawal for patients with&#xD;
      medication overuse, but it is also confirmed that patients have to be carefully followed&#xD;
      after withdrawal to avoid relapses and to improve the clinical benefit of the therapeutic&#xD;
      approach. Clinical results can be improved when traditional therapies are combined with&#xD;
      behavioral approaches in particular mindfulness, that help patient to become more conscious&#xD;
      about their symptoms and able to manage pain without medication. As the emergency situation&#xD;
      due to the Corona-virus pandemic phenomenon in Italy, the regular clinical practice adopted&#xD;
      for patients with CM-MO has changed in the last weeks: patients cannot come to the hospital&#xD;
      for the withdrawal iv therapy and for regular follow up as the reduced mobility due to the&#xD;
      emergency in particular in the Lombardia region, but all over Italy. So the investigators&#xD;
      propose a pilot study to enforce the application of a Home-program for the withdrawal&#xD;
      procedure for patients and the use of technology like smartphone and video calls so that&#xD;
      patients can continue to be followed in their therapeutic process by using behavioral support&#xD;
      and mindfulness practice. Patients will perform the withdrawal program at home, by oral&#xD;
      administration of therapies, with specific instructions and education. Also the information&#xD;
      for behavioral approach and mindfulness practice will be given, to use every day at home.&#xD;
      Daily standardized mindfulness sessions of 12 minutes on their smartphone will be combined&#xD;
      with weekly video-call to evaluate the clinical condition and to encourage the use strategies&#xD;
      for pain management. Face-to-face visits at the follow up every three months will be&#xD;
      scheduled. This modality will allow the patients to continue their therapeutic process and to&#xD;
      be regularly followed during the one year after withdrawal.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background and significance Medication Overuse Headache (MOH) is a disabling pain syndrome&#xD;
      with a prevalence of 2% in the general population, and which affects patients suffering from&#xD;
      primary headaches, mainly those with Chronic Migraine (CM). This condition is very difficult&#xD;
      to treat. The literature of the last decades confirmed the need to stop overuse through&#xD;
      withdrawal (or detoxification programs) as an essential step in the treatment strategy , and&#xD;
      high rates of successful outcomes are reported by several studies and reviews, although not&#xD;
      all patients receiving treatment are able to stop MO or to reduce significantly the frequency&#xD;
      of headaches. Remission rates range from 60% to 83% in studies with a 1-year follow-up, with&#xD;
      an average relapse rate into MOH of 32.8% in a review on several studies from different&#xD;
      countries, which is similar to the relapse into CM of 21.5% and into MOH of 33.9% found in a&#xD;
      sample from our group . Literature data showed that patients need to be carefully followed&#xD;
      after withdrawal to avoid relapses in overuse and to improve the clinical benefit, adding&#xD;
      anti-migraine prophylaxi . Furthermore, different clinical experiences confirmed the&#xD;
      effectiveness of interventions based on out-patient withdrawal programs and education and&#xD;
      support to the correct use of medications to patients, and published evidence - also from our&#xD;
      research group - supports the role of standardized behavioural approaches . The aspect of&#xD;
      feasibility of these treatments is not regularly reported in published studies, but it can be&#xD;
      estimated that a proportion of patients discontinue the treatment protocols, with a drop-out&#xD;
      rate around 15-20% at one year from withdrawal., as it was 11% after 6 months, and 18% after&#xD;
      1 year in the seminal study by Katsarawa et al, and 9% after one year from withdrawal in a&#xD;
      previous study from our research group . According to our protocols at the Headache Center,&#xD;
      the withdrawal program is performed at hospital, either in an in-patient setting or in&#xD;
      day-hospital setting. This program includes abrupt interruption of the overused drugs,&#xD;
      intravenous therapy, educational support, rescue treatments for severe headaches, and&#xD;
      prescription of a specific pharmacological prophylaxis for migraine prevention. Furthermore,&#xD;
      standardized behavioural therapies are used during the treatment period, and during the&#xD;
      follow up, particularly by approaches based on mindfulness practice - which usually delivered&#xD;
      in groups of 4 - 8 patients . This approach may be particularly useful in helping patients to&#xD;
      obtain a better outcome. All the above discussed considerations are even more relevant in&#xD;
      this emergency situation due to the Corona-virus pandemic phenomenon in Italy, with its&#xD;
      consequences on mobility of patients and clinical practice. In order to promote different&#xD;
      modalities to respond to the needs of patients suffering from this disabling condition during&#xD;
      the emergency, exercise-based telemedicine and smartphone applications seem very appropriate,&#xD;
      as they have been recently tested in the management of chronic pain conditions . This&#xD;
      preliminary study will be performed considering that the Covid-19 emergency reduced&#xD;
      significantly our possibility to hospitalize patients for withdrawal treatments as well as&#xD;
      the mobility of patients, particularly those living in other Italian regions than Lombardy,&#xD;
      and in view of providing an effective and somewhat innovative treatment program for MOH and&#xD;
      CM patients. The proposed treatment intervention is based on our experience, and on published&#xD;
      reports, but it specifically includes a home based withdrawal program, several visits&#xD;
      performed as Video calls, and educational and support strategies aimed to develop skills to&#xD;
      reduce overuse and to cope with pain by a standardized behavioural approach based on&#xD;
      mindfulness - which will be delivered mainly by telemedicine and smartphone applications. The&#xD;
      aim of this pilot study is to assess the feasibility and the effectiveness at long-term on&#xD;
      relevant outcomes of a specific protocol, designed to be appropriate during the emergency&#xD;
      situation due to COVID-19 epidemic, by an approach that is alternative to current practice,&#xD;
      particularly as far as avoiding the need for hospitalization, reducing face-to-face hospital&#xD;
      visits taking advantage of facilities offered by new technologies, besides including&#xD;
      innovative and emerging treatment choices, namely a behavioural approach base on mindfulness.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>withdrawal program will be performed at home</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Drop out rates</measure>
    <time_frame>at 12 months</time_frame>
    <description>Drop-out rates after withdrawal treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absence of Medication Overuse Headache (MOH)</measure>
    <time_frame>at 12 months from withdrawal program (assessed by Daily Diary Card)</time_frame>
    <description>Percentages of patients with absence of Medication Overuse Headache</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Migraine, Hemicrania</condition>
  <arm_group>
    <arm_group_label>Symptomatic drugs - bridge theray - mindfu</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>abrupt withdrawal of overuse symptomatic drugs, with possibility to use indomethacin suppository 50-100 mg or an oral triptan, on maximum 3 days/10 days, only in case of very severe headache- and to use metoclopramide i.m. injection in case of vomiting;&#xD;
oral administration of a bridge therapy to reduce the withdrawal symptoms and rebound headache (prednisone 25 mg , 2 tablets after breakfast for 5 days, one tablet for 3 days, half tablet for 2 days ; bromazepam 1.5 mg, 1 tablet after breakfast, lunch and dinner for every day; pantoprazole 40 mg, 1 tablet after dinner every day);&#xD;
mindfulness practice daily with standard sessions by smartphone 6 minutes per day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Symptomatic drugs</intervention_name>
    <description>indomethacin suppository 50-100 mg or an oral triptan, on maximum 3 days/10 days, only in case of very severe headache- and to use metoclopramide</description>
    <arm_group_label>Symptomatic drugs - bridge theray - mindfu</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bridge therapy</intervention_name>
    <description>prednisone 25 mg , 2 tablets after breakfast for 5 days, one tablet for 3 days, half tablet for 2 days ; bromazepam 1.5 mg, 1 tablet after breakfast, lunch and dinner for every day; pantoprazole 40 mg, 1 tablet after dinner every day</description>
    <arm_group_label>Symptomatic drugs - bridge theray - mindfu</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Mindfulness program</intervention_name>
    <description>home based withdrawal program</description>
    <arm_group_label>Symptomatic drugs - bridge theray - mindfu</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        age &gt;18 yrs diagnosis of MOH and CM (1) written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        co-existent severe medical or psychiatric illnesses, documented by specific previous&#xD;
        diagnoses seizures use of opioids&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Licia Grazzi, MD</last_name>
    <phone>+39022394</phone>
    <phone_ext>2366</phone_ext>
    <email>licia.grazzi@istituto-besta.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Renato Mantegazza, MD</last_name>
    <phone>+39022394</phone>
    <phone_ext>2321</phone_ext>
    <email>crc@istituto-besta.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Neurologico C. Besta, Neuroalgology Unit</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Licia Grazzi, MD</last_name>
      <email>licia.grazzi@istituto-besta.it</email>
    </contact>
    <investigator>
      <last_name>Licia Grazzi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>October 8, 2020</last_update_submitted>
  <last_update_submitted_qc>October 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Headache Disorders, Secondary</mesh_term>
    <mesh_term>Migraine Disorders</mesh_term>
    <mesh_term>Emergencies</mesh_term>
    <mesh_term>Headache</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04410536
org study id: MOH
nct id: NCT04410536
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Medication Overuse Headache (MOH) is a disabling condition that affects the 2% of migraine
      population. Medication overuse (MO) makes this condition very difficult to treat. The
      literature of the last decades confirm the efficacy of withdrawal for patients with
      medication overuse, but it is also confirmed that patients have to be carefully followed
      after withdrawal to avoid relapses and to improve the clinical benefit of the therapeutic
      approach. Clinical results can be improved when traditional therapies are combined with
      behavioral approaches in particular mindfulness, that help patient to become more conscious
      about their symptoms and able to manage pain without medication. As the emergency situation
      due to the Corona-virus pandemic phenomenon in Italy, the regular clinical practice adopted
      for patients with CM-MO has changed in the last weeks: patients cannot come to the hospital
      for the withdrawal iv therapy and for regular follow up as the reduced mobility due to the
      emergency in particular in the Lombardia region, but all over Italy. So the investigators
      propose a pilot study to enforce the application of a Home-program for the withdrawal
      procedure for patients and the use of technology like smartphone and video calls so that
      patients can continue to be followed in their therapeutic process by using behavioral support
      and mindfulness practice. Patients will perform the withdrawal program at home, by oral
      administration of therapies, with specific instructions and education. Also the information
      for behavioral approach and mindfulness practice will be given, to use every day at home.
      Daily standardized mindfulness sessions of 12 minutes on their smartphone will be combined
      with weekly video-call to evaluate the clinical condition and to encourage the use strategies
      for pain management. Face-to-face visits at the follow up every three months will be
      scheduled. This modality will allow the patients to continue their therapeutic process and to
      be regularly followed during the one year after withdrawal.
Background and significance Medication Overuse Headache (MOH) is a disabling pain syndrome
      with a prevalence of 2% in the general population, and which affects patients suffering from
      primary headaches, mainly those with Chronic Migraine (CM). This condition is very difficult
      to treat. The literature of the last decades confirmed the need to stop overuse through
      withdrawal (or detoxification programs) as an essential step in the treatment strategy , and
      high rates of successful outcomes are reported by several studies and reviews, although not
      all patients receiving treatment are able to stop MO or to reduce significantly the frequency
      of headaches. Remission rates range from 60% to 83% in studies with a 1-year follow-up, with
      an average relapse rate into MOH of 32.8% in a review on several studies from different
      countries, which is similar to the relapse into CM of 21.5% and into MOH of 33.9% found in a
      sample from our group . Literature data showed that patients need to be carefully followed
      after withdrawal to avoid relapses in overuse and to improve the clinical benefit, adding
      anti-migraine prophylaxi . Furthermore, different clinical experiences confirmed the
      effectiveness of interventions based on out-patient withdrawal programs and education and
      support to the correct use of medications to patients, and published evidence - also from our
      research group - supports the role of standardized behavioural approaches . The aspect of
      feasibility of these treatments is not regularly reported in published studies, but it can be
      estimated that a proportion of patients discontinue the treatment protocols, with a drop-out
      rate around 15-20% at one year from withdrawal., as it was 11% after 6 months, and 18% after
      1 year in the seminal study by Katsarawa et al, and 9% after one year from withdrawal in a
      previous study from our research group . According to our protocols at the Headache Center,
      the withdrawal program is performed at hospital, either in an in-patient setting or in
      day-hospital setting. This program includes abrupt interruption of the overused drugs,
      intravenous therapy, educational support, rescue treatments for severe headaches, and
      prescription of a specific pharmacological prophylaxis for migraine prevention. Furthermore,
      standardized behavioural therapies are used during the treatment period, and during the
      follow up, particularly by approaches based on mindfulness practice - which usually delivered
      in groups of 4 - 8 patients . This approach may be particularly useful in helping patients to
      obtain a better outcome. All the above discussed considerations are even more relevant in
      this emergency situation due to the Corona-virus pandemic phenomenon in Italy, with its
      consequences on mobility of patients and clinical practice. In order to promote different
      modalities to respond to the needs of patients suffering from this disabling condition during
      the emergency, exercise-based telemedicine and smartphone applications seem very appropriate,
      as they have been recently tested in the management of chronic pain conditions . This
      preliminary study will be performed considering that the Covid-19 emergency reduced
      significantly our possibility to hospitalize patients for withdrawal treatments as well as
      the mobility of patients, particularly those living in other Italian regions than Lombardy,
      and in view of providing an effective and somewhat innovative treatment program for MOH and
      CM patients. The proposed treatment intervention is based on our experience, and on published
      reports, but it specifically includes a home based withdrawal program, several visits
      performed as Video calls, and educational and support strategies aimed to develop skills to
      reduce overuse and to cope with pain by a standardized behavioural approach based on
      mindfulness - which will be delivered mainly by telemedicine and smartphone applications. The
      aim of this pilot study is to assess the feasibility and the effectiveness at long-term on
      relevant outcomes of a specific protocol, designed to be appropriate during the emergency
      situation due to COVID-19 epidemic, by an approach that is alternative to current practice,
      particularly as far as avoiding the need for hospitalization, reducing face-to-face hospital
      visits taking advantage of facilities offered by new technologies, besides including
      innovative and emerging treatment choices, namely a behavioural approach base on mindfulness.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: withdrawal program will be performed at home
primary purpose: Treatment
masking: None (Open Label)
measure: Drop out rates
time frame: at 12 months
description: Drop-out rates after withdrawal treatment
measure: Absence of Medication Overuse Headache (MOH)
time frame: at 12 months from withdrawal program (assessed by Daily Diary Card)
description: Percentages of patients with absence of Medication Overuse Headache
arm group label: Symptomatic drugs - bridge theray - mindfu
arm group type: Other
description: abrupt withdrawal of overuse symptomatic drugs, with possibility to use indomethacin suppository 50-100 mg or an oral triptan, on maximum 3 days/10 days, only in case of very severe headache- and to use metoclopramide i.m. injection in case of vomiting;
oral administration of a bridge therapy to reduce the withdrawal symptoms and rebound headache (prednisone 25 mg , 2 tablets after breakfast for 5 days, one tablet for 3 days, half tablet for 2 days ; bromazepam 1.5 mg, 1 tablet after breakfast, lunch and dinner for every day; pantoprazole 40 mg, 1 tablet after dinner every day);
mindfulness practice daily with standard sessions by smartphone 6 minutes per day.
intervention type: Drug
intervention name: Symptomatic drugs
description: indomethacin suppository 50-100 mg or an oral triptan, on maximum 3 days/10 days, only in case of very severe headache- and to use metoclopramide
arm group label: Symptomatic drugs - bridge theray - mindfu
intervention type: Drug
intervention name: Bridge therapy
description: prednisone 25 mg , 2 tablets after breakfast for 5 days, one tablet for 3 days, half tablet for 2 days ; bromazepam 1.5 mg, 1 tablet after breakfast, lunch and dinner for every day; pantoprazole 40 mg, 1 tablet after dinner every day
arm group label: Symptomatic drugs - bridge theray - mindfu
intervention type: Behavioral
intervention name: Mindfulness program
description: home based withdrawal program
arm group label: Symptomatic drugs - bridge theray - mindfu
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Licia Grazzi, MD
phone: +39022394
phone ext: 2366
email: licia.grazzi@istituto-besta.it
last name: Renato Mantegazza, MD
phone: +39022394
phone ext: 2321
email: crc@istituto-besta.it
facility: 
status: Recruiting
contact: 
investigator: 
country: Italy
responsible party type: Sponsor
mesh term: Headache Disorders, Secondary
mesh term: Migraine Disorders
mesh term: Emergencies
mesh term: Headache
sharing ipd: No