<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/NCT04406376</url>
  </required_header>
  <id_info>
    <org_study_id>CMC-20-0001-CTIL</org_study_id>
    <nct_id>NCT04406376</nct_id>
  </id_info>
  <brief_title>Do We Need to Taper Down Steroid Therapy for Bell's Palsy</brief_title>
  <official_title>Do We Need to Taper Down Steroid Therapy for Bell's Palsy: A Prospective Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Carmel Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Carmel Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bell's palsy [BP] is defined as acute idiopathic peripheral facial palsy or paralysis.&#xD;
&#xD;
      Additional symptoms frequently include pain around or behind the ear, impaired tolerance to&#xD;
      ordinary levels of noise and disturbed sense of taste on the same side. It affects men and&#xD;
      women more or less equally.&#xD;
&#xD;
      There is a consensus in the literature regarding the importance of steroid treatment for&#xD;
      improving recovery rates and sequela of BP. Moreover, there is increasing level of high&#xD;
      quality of evidence in recent years for a combined antiviral and steroids treatment for&#xD;
      severe BP (House Brackmann [HB] 5-6).&#xD;
&#xD;
      Adverse effects (AEs) were reported in 1-12% of patients treated with steroids, antivirals or&#xD;
      placebo. The AEs reported were dyspepsia, loss of blood sugar control, headache, fatigue,&#xD;
      dizziness and insomnia, recurrent duodenal ulcers, mood swings, and acute psychosis. All&#xD;
      effects resolved when treatment was stopped.&#xD;
&#xD;
      Although steroid and antivirals are widely used for BP, there is a high variability of&#xD;
      steroids treatment, both in the dosage given and in the way of tapering down.&#xD;
&#xD;
      Among the different steroid regimens used were: prednisone 1 mg/kg for 5 days tapered to 10&#xD;
      mg/day for remaining 5 days; prednisone (1 mg/kg for 10 days then tapered to zero over the&#xD;
      next 6 days); prednisolone 60 mg for 5 days, 30 mg for 3 days, and 10 mg for 2 days.&#xD;
&#xD;
      House-Brackmann (HB) system is widely used for facial function assessment. It is based on a&#xD;
      six-grade score, where grade I is normal function, grade VI is complete absence of facial&#xD;
      motor function, and grades II to V are intermediate.&#xD;
&#xD;
      Steroid-induced side effects generally require tapering of the drug as soon as the disease&#xD;
      being treated is under control. Tapering must be done carefully to avoid both recurrent&#xD;
      activity of the underlying disease and possible cortisol deficiency resulting from&#xD;
      hypothalamic-pituitary-adrenal axis (HPA) suppression. However, according to a review by&#xD;
      Furst et al (2019), a patient who has received any dose of glucocorticoid for less than 3&#xD;
      weeks or patients treated with alternate-day prednisone at a dose of less than 10 mg (or its&#xD;
      equivalent) are unlikely for HPA suppression. They concluded that short-term glucocorticoid&#xD;
      therapy (up to three weeks), even if at a fairly high dose, can simply be stopped and need&#xD;
      not to be tapered..&#xD;
&#xD;
      According to the above, the investigators assume that a rapid withdrawal of steroids after&#xD;
      short course of treatment for BP should neither influence the efficacy or safety of&#xD;
      treatment.&#xD;
&#xD;
      Finally, steroid regimen may be hard to follow for some patients and can results in confusion&#xD;
      and frustration. Simplifying steroid regimen, such as skipping withdrawal if not necessary,&#xD;
      may solve this problem.&#xD;
&#xD;
      The objective of our study is to determine the effectiveness and safety of prednisone&#xD;
      treatment with no tapering down for Bell's Palsy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A prospective randomized controlled trial of adult patients diagnosed with BP in the&#xD;
      otolaryngology emergency department within 72 hours of symptoms onset.&#xD;
&#xD;
      Patients will be randomized to receive one of the following steroids regimens:&#xD;
&#xD;
        1. Prednisone 1 mg/kg (max. 60 mg) daily for 7 days, 40 mg for 2 days, 20 mg for 2 days&#xD;
           (Total 11 days)&#xD;
&#xD;
        2. Prednisone 1 mg/kg (max. 60 mg) daily for 7 days (Total 7 days)&#xD;
&#xD;
      In addition, both groups will receive the following treatment when indicated:&#xD;
&#xD;
        -  Mosturizing eye drops for 14 days or until complete recovery (HB-1)&#xD;
&#xD;
        -  Mosturizing eye gel for 14 days or until complete recovery (HB-1)&#xD;
&#xD;
        -  Omepradex once daily during prednisone treatment (unless the patient receives chronic&#xD;
           treatment with any proton pump inhibitor).&#xD;
&#xD;
        -  Acyclovir for 7 days in cases of severe BP (HB 5-6).&#xD;
&#xD;
      Patients' follow-up visits: 14 days, 1 month, 3 months. If recovery will be completed before&#xD;
      1 month, no more follow up visits will be taken.&#xD;
&#xD;
      In addition, side effects of prednisone use will be assessed as well as compliance to therapy&#xD;
      and duration of additional symptoms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 12, 2020</start_date>
  <completion_date type="Anticipated">August 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients will be randomized to recieve one of the following steroids regimens:&#xD;
Prednisone 1 mg/kg (max. 60 mg) daily for 7 days, 40 mg for 2 days, 20 mg for 2 days (Total 11 days)&#xD;
Prednisone 1 mg/kg (max. 60 mg) daily for 7 days (Total 7 days)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>House-Brackmann scale</measure>
    <time_frame>14 days- 90 days</time_frame>
    <description>Time to complete recovery (Grade I- normal function) of facial palsy using the House-Brackmann scale for assessment. The scale is assessed by an ENT physician in four standard poses: at rest, with a forced smile, with raised eyebrows, and with eyes tightly closed and scored between I (normal function)- VI (complete palsy, worse outcome).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to incomplete recovery</measure>
    <time_frame>14 days- 90 days</time_frame>
    <description>Time to presentation of House-Brackmann Grade II or worse and the difference between House-Brackmann scores between visits (i.e improvement from House-Brackmann 4 to 2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Motor Synkinesis</measure>
    <time_frame>14 days- 90 days</time_frame>
    <description>Occurrence of abnormal synchronization of facial movement where muscles, other than those intended, contract together during a particular movement pattern.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of neurological symptoms</measure>
    <time_frame>14 days- 90 days</time_frame>
    <description>Duration of hypoesthesia (trigeminal/ glossopharyngeal), periauricular pain, dysgusia, hyperacusis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ocular symptoms</measure>
    <time_frame>14 days- 90 days</time_frame>
    <description>Duration of dryness, epiphora, itching, eye pain, etc</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects of prednisone use</measure>
    <time_frame>14 days- 90 days</time_frame>
    <description>Incidence of dyspepsia, loss of blood sugar control, headache, fatigue, dizziness and insomnia, recurrent duodenal ulcers, mood swings, acute psychosis, etc</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">124</enrollment>
  <condition>Bell Palsy</condition>
  <arm_group>
    <arm_group_label>Tapering Down of Steroids</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Prednisone 1 mg/kg (max. 60 mg) daily for 7 days, 40 mg for 2 days, 20 mg for 2 days (Total 11 days)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Tapering Down of Steroids</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Prednisone 1 mg/kg (max. 60 mg) daily for 7 days (Total 7 days)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone tablet</intervention_name>
    <description>Treatment of Bell's Palsy with prednisone, with or without tapering down.</description>
    <arm_group_label>No Tapering Down of Steroids</arm_group_label>
    <arm_group_label>Tapering Down of Steroids</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients (≥18 years) diagnosed with BP within 72 hour of onset.&#xD;
&#xD;
          2. Adult patients willing to get treatment, attending follow up visits and signing&#xD;
             informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients treated with antivirals (i.e acyclovir) for any reason simultaneously, such&#xD;
             as Herpes Zoster (Ramsay- Hunt syndrome).&#xD;
&#xD;
          2. Palsy onset &gt; 72 hours before diagnosis or unknown onset.&#xD;
&#xD;
          3. Previous episodes of BP.&#xD;
&#xD;
          4. Patients suspected for hypothalamic-pituitary-adrenal (HPA) axis suppression who have&#xD;
             to be cautiously tapered due to high risk for adrenal insufficiency: steroid treatment&#xD;
             in any dosage for more the 3 weeks (due to other indication) or cushingoid appearance.&#xD;
&#xD;
          5. Contraindication for steroid use: uncontrolled diabetes or hypertension, psychosis,&#xD;
             peptic ulcer or upper GI bleeding, liver cirrhosis or portal hypertension, known&#xD;
             allergy to prednisone, etc. Any case in which steroid treatment was stopped earlier&#xD;
             than planned by the patient or the physician.&#xD;
&#xD;
          6. Any conditions suspicious for non-idiopathic facial palsy: chronic otitis media, acute&#xD;
             otitis media, mastoiditis, temporal bone/middle ear trauma, other cranial nerve&#xD;
             neuropathies (i.e cranial nerve VIII), cerebrovascular disorders, tumor affecting&#xD;
             facial nerve (i.e, parotid malignancy, schwannoma) or systemic causes (i.e multiple&#xD;
             sclerosis, meningitis, sarcoidosis, HIV infection, etc).&#xD;
&#xD;
          7. Patients with low compliance for treatment according to the physician.&#xD;
&#xD;
          8. Pregnancy or breast-feeding patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yoav Yanir, MD</last_name>
    <role>Study Director</role>
    <affiliation>Carmel Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Itai Margulis, MD</last_name>
    <phone>972-48250279</phone>
    <email>itayma@clalit.gov.il</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Raanan Cohen-Kerem, MD</last_name>
    <phone>972-48250005</phone>
    <email>raanan@clalit.org.il</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Lady Davies Carmel Medical Center. Department of Otolaryngology, Head and Neck Surgery</name>
      <address>
        <city>Haifa</city>
        <state>North</state>
        <zip>3436212</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Itai Margulis, MD</last_name>
      <phone>+97248250279</phone>
      <email>itayma@clalit.org.il</email>
    </contact>
    <contact_backup>
      <last_name>Yoav Yanir, MD</last_name>
      <phone>+97248250433</phone>
      <email>yoavya@clalit.org.il</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>May 9, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>July 27, 2020</last_update_submitted>
  <last_update_submitted_qc>July 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Carmel Medical Center</investigator_affiliation>
    <investigator_full_name>Itai Margulis</investigator_full_name>
    <investigator_title>Intern, Department of Otolaryngology Head and Neck Surgery, Principal Investigator, Medical Doctor</investigator_title>
  </responsible_party>
  <keyword>Tapering Down</keyword>
  <keyword>Adverse Effects</keyword>
  <keyword>House Brackmann</keyword>
  <keyword>Steroids</keyword>
  <keyword>Prednisone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bell Palsy</mesh_term>
    <mesh_term>Facial Paralysis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04406376
org study id: CMC-20-0001-CTIL
nct id: NCT04406376
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Bell's palsy [BP] is defined as acute idiopathic peripheral facial palsy or paralysis.

      Additional symptoms frequently include pain around or behind the ear, impaired tolerance to
      ordinary levels of noise and disturbed sense of taste on the same side. It affects men and
      women more or less equally.

      There is a consensus in the literature regarding the importance of steroid treatment for
      improving recovery rates and sequela of BP. Moreover, there is increasing level of high
      quality of evidence in recent years for a combined antiviral and steroids treatment for
      severe BP (House Brackmann [HB] 5-6).

      Adverse effects (AEs) were reported in 1-12% of patients treated with steroids, antivirals or
      placebo. The AEs reported were dyspepsia, loss of blood sugar control, headache, fatigue,
      dizziness and insomnia, recurrent duodenal ulcers, mood swings, and acute psychosis. All
      effects resolved when treatment was stopped.

      Although steroid and antivirals are widely used for BP, there is a high variability of
      steroids treatment, both in the dosage given and in the way of tapering down.

      Among the different steroid regimens used were: prednisone 1 mg/kg for 5 days tapered to 10
      mg/day for remaining 5 days; prednisone (1 mg/kg for 10 days then tapered to zero over the
      next 6 days); prednisolone 60 mg for 5 days, 30 mg for 3 days, and 10 mg for 2 days.

      House-Brackmann (HB) system is widely used for facial function assessment. It is based on a
      six-grade score, where grade I is normal function, grade VI is complete absence of facial
      motor function, and grades II to V are intermediate.

      Steroid-induced side effects generally require tapering of the drug as soon as the disease
      being treated is under control. Tapering must be done carefully to avoid both recurrent
      activity of the underlying disease and possible cortisol deficiency resulting from
      hypothalamic-pituitary-adrenal axis (HPA) suppression. However, according to a review by
      Furst et al (2019), a patient who has received any dose of glucocorticoid for less than 3
      weeks or patients treated with alternate-day prednisone at a dose of less than 10 mg (or its
      equivalent) are unlikely for HPA suppression. They concluded that short-term glucocorticoid
      therapy (up to three weeks), even if at a fairly high dose, can simply be stopped and need
      not to be tapered..

      According to the above, the investigators assume that a rapid withdrawal of steroids after
      short course of treatment for BP should neither influence the efficacy or safety of
      treatment.

      Finally, steroid regimen may be hard to follow for some patients and can results in confusion
      and frustration. Simplifying steroid regimen, such as skipping withdrawal if not necessary,
      may solve this problem.

      The objective of our study is to determine the effectiveness and safety of prednisone
      treatment with no tapering down for Bell's Palsy.
A prospective randomized controlled trial of adult patients diagnosed with BP in the
      otolaryngology emergency department within 72 hours of symptoms onset.

      Patients will be randomized to receive one of the following steroids regimens:

        1. Prednisone 1 mg/kg (max. 60 mg) daily for 7 days, 40 mg for 2 days, 20 mg for 2 days
           (Total 11 days)

        2. Prednisone 1 mg/kg (max. 60 mg) daily for 7 days (Total 7 days)

      In addition, both groups will receive the following treatment when indicated:

        -  Mosturizing eye drops for 14 days or until complete recovery (HB-1)

        -  Mosturizing eye gel for 14 days or until complete recovery (HB-1)

        -  Omepradex once daily during prednisone treatment (unless the patient receives chronic
           treatment with any proton pump inhibitor).

        -  Acyclovir for 7 days in cases of severe BP (HB 5-6).

      Patients' follow-up visits: 14 days, 1 month, 3 months. If recovery will be completed before
      1 month, no more follow up visits will be taken.

      In addition, side effects of prednisone use will be assessed as well as compliance to therapy
      and duration of additional symptoms.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be randomized to recieve one of the following steroids regimens:
Prednisone 1 mg/kg (max. 60 mg) daily for 7 days, 40 mg for 2 days, 20 mg for 2 days (Total 11 days)
Prednisone 1 mg/kg (max. 60 mg) daily for 7 days (Total 7 days)
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: House-Brackmann scale
time frame: 14 days- 90 days
description: Time to complete recovery (Grade I- normal function) of facial palsy using the House-Brackmann scale for assessment. The scale is assessed by an ENT physician in four standard poses: at rest, with a forced smile, with raised eyebrows, and with eyes tightly closed and scored between I (normal function)- VI (complete palsy, worse outcome).
measure: Time to incomplete recovery
time frame: 14 days- 90 days
description: Time to presentation of House-Brackmann Grade II or worse and the difference between House-Brackmann scores between visits (i.e improvement from House-Brackmann 4 to 2)
measure: Occurrence of Motor Synkinesis
time frame: 14 days- 90 days
description: Occurrence of abnormal synchronization of facial movement where muscles, other than those intended, contract together during a particular movement pattern.
measure: Duration of neurological symptoms
time frame: 14 days- 90 days
description: Duration of hypoesthesia (trigeminal/ glossopharyngeal), periauricular pain, dysgusia, hyperacusis
measure: Duration of ocular symptoms
time frame: 14 days- 90 days
description: Duration of dryness, epiphora, itching, eye pain, etc
measure: Adverse effects of prednisone use
time frame: 14 days- 90 days
description: Incidence of dyspepsia, loss of blood sugar control, headache, fatigue, dizziness and insomnia, recurrent duodenal ulcers, mood swings, acute psychosis, etc
arm group label: Tapering Down of Steroids
arm group type: Active Comparator
description: Prednisone 1 mg/kg (max. 60 mg) daily for 7 days, 40 mg for 2 days, 20 mg for 2 days (Total 11 days)
arm group label: No Tapering Down of Steroids
arm group type: Active Comparator
description: Prednisone 1 mg/kg (max. 60 mg) daily for 7 days (Total 7 days)
intervention type: Drug
intervention name: Prednisone tablet
description: Treatment of Bell's Palsy with prednisone, with or without tapering down.
arm group label: No Tapering Down of Steroids
arm group label: Tapering Down of Steroids
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Yoav Yanir, MD
role: Study Director
affiliation: Carmel Medical Center
last name: Itai Margulis, MD
phone: 972-48250279
email: itayma@clalit.gov.il
last name: Raanan Cohen-Kerem, MD
phone: 972-48250005
email: raanan@clalit.org.il
facility: 
status: Recruiting
contact: 
contact backup: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: Carmel Medical Center
investigator full name: Itai Margulis
investigator title: Intern, Department of Otolaryngology Head and Neck Surgery, Principal Investigator, Medical Doctor
mesh term: Bell Palsy
mesh term: Facial Paralysis
mesh term: Prednisone