<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/NCT02256215</url>
  </required_header>
  <id_info>
    <org_study_id>RLSD-1234</org_study_id>
    <nct_id>NCT02256215</nct_id>
  </id_info>
  <brief_title>Vitamin D in the Treatment of Primary Restless Legs Syndrome</brief_title>
  <official_title>Vitamin D in the Treatment of Primary Restless Legs Syndrome: 12 Weeks, Triple-blinded, Randomized, Placebo-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King Abdulaziz University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>King AbdulAziz City for Science and Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>King Abdulaziz University</source>
  <brief_summary>
    <textblock>
      Restless Legs Syndrome (RLS) is a sensorimotor disorder that syndrome may substantially&#xD;
      interfere with normal sleep, leading to significant impairment in patients' productivity and&#xD;
      quality of life.&#xD;
&#xD;
      The most common and potent of all treatment regimens are the dopaminergic agonist agents,&#xD;
      which carry serious adverse events in their prolonged use despite their augmentation. A few&#xD;
      basic studies have suggested a potential relationship between vitamin D and RLS. It has been&#xD;
      implicated that dopaminergic system dysfunction plays a role in the development of RLS, while&#xD;
      vitamin D has a protective effect on that system. This has been further substantiated by few&#xD;
      clinical observations that showed prompt improvement of RLS patients upon receiving&#xD;
      dopaminergic agents such as carbamazepine. Other studies have revealed low serum levels of&#xD;
      vitamin D in RLS patients, along with remarkable improvement after vitamin D replacement&#xD;
      therapy, as has been demonstrated in a recent pilot study.&#xD;
&#xD;
      This collectively points at vitamin D as a potential, more natural and safer treatment option&#xD;
      for those suffering from RLS. However, the role of vitamin D in RLS has not been effectively&#xD;
      investigated. The aim of this 12-week, triple-blinded, randomized, placebo-controlled trial&#xD;
      is to confirm the relationship between vitamin D deficiency and RLS and hence elucidate the&#xD;
      efficacy of vitamin D replacement therapy in reducing the severity of RLS, with predictions&#xD;
      that the results will contribute to better understanding of the disease and its management.&#xD;
&#xD;
      Methods and Materials: This 12-week, double-blinded, randomized, placebo-controlled trial is&#xD;
      take place over a duration of 2 years. It will be held in the city of Jeddah to assess a&#xD;
      sample of Saudi residents of the Western region.&#xD;
&#xD;
      It is comprised of a number of visits, with the first one consisting of a questionnaire that&#xD;
      is to be answered regarding RLS, physical examination, electromyography, the objective&#xD;
      multiple Suggested Immobilization test, and blood tests. The main purpose of the second visit&#xD;
      is to establish a diagnosis of RLS.&#xD;
&#xD;
      Clinic visits number 3 through 6 comprise the pre-randomizaiton phase. Their purpose is to&#xD;
      determine the patient's adherence to trial procedures and pharmacological treatment.&#xD;
&#xD;
      Then, patients are to visit the clinic every two weeks for the first two months, then at week&#xD;
      12. Patients will be assessed in regards to treatment response and adverse effects through&#xD;
      history and physical examination along with further blood tests.&#xD;
&#xD;
      Aim: to confirm the relationship between vitamin D deficiency and RLS and hence elucidate the&#xD;
      efficacy of vitamin D replacement therapy in reducing the severity of RLS, with predictions&#xD;
      that the results will contribute to better understanding of the disease and its management.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>December 2015</start_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in The International Restless Legs Scale (IRLS) total score</measure>
    <time_frame>12 weeks</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">106</enrollment>
  <condition>Restless Legs Syndrome</condition>
  <arm_group>
    <arm_group_label>Vitamin D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>• All patients will have their serum vitamin D levels measured at the baseline visit. Those assigned to the treatment arm (group A) will receive either 50,000 international units of vitamin D3 by mouth once or more per week for six to eight weeks, then 800 to 1000 (or more) international units of vitamin D3 daily thereafter, this is according to the recommendations of the Endocrine Society clinical practice guideline 2011. Group B patients will receive placebo supplements identical in appearance to the vitamin D supplements.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D</intervention_name>
    <arm_group_label>Vitamin D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Newly diagnosed or already diagnosed patients with primary RLS and vitamin D&#xD;
             deficiency.&#xD;
&#xD;
          2. Patients that are not currently receiving any treatment for RLS or vitamin D&#xD;
             replacement therapy.&#xD;
&#xD;
          3. Patients from 18 to 75 years old.&#xD;
&#xD;
          4. Patients otherwise are in good general health.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients diagnosed with secondary RLS. i.e.: patients with:&#xD;
&#xD;
        1. Iron deficiency anemia 2. End-stage renal disease. 3. Diabetes mellitus (DM). 4.&#xD;
        Peripheral neuropathy. 5. Multiple sclerosis (MS). 6. Pregnancy.&#xD;
&#xD;
        2. Patients with other mimicking disorders or primary sleep disorders. E.g.:&#xD;
&#xD;
          1. Arthritis.&#xD;
&#xD;
          2. Deep venous thrombosis.&#xD;
&#xD;
          3. Varicose veins or venous insufficiency.&#xD;
&#xD;
          4. Habitual foot tapping.&#xD;
&#xD;
        3. Patients receiving medications that can trigger RLS. i.e.:&#xD;
&#xD;
          1. Anti hypertensive medications. E.g. Use of thiazide diuretics at a total dose greater&#xD;
             than 37.5 mg/day.&#xD;
&#xD;
          2. Anti convulsion medications.e.g. Use of anticonvulsant drug started within 6 months of&#xD;
             screening. Stable regimen of anticonvulsants is allowed.&#xD;
&#xD;
          3. Antinausea drugs (prochlorperazine or metoclopramide).&#xD;
&#xD;
          4. Antipsychotic drugs (haloperidol or phenothiazine derivatives).&#xD;
&#xD;
          5. Anti depressants (SSRIs).&#xD;
&#xD;
          6. Antihistamines as in cold and allergy medications.&#xD;
&#xD;
        4. Patients with current medications or conditions that would interfere with vitamin D&#xD;
        absorption:&#xD;
&#xD;
        1. Celiac disease. 2. Chron's disease. 3. Chronic pancreatitis. 4. Cystic fibrosis. 5.&#xD;
        Weight-loss drug e.g. orlistat. 6. Cholesterol-lowering drug e.g. cholestyramine&#xD;
&#xD;
        5. Patients with contraindications for vitamin D supplements. i.e.:&#xD;
&#xD;
          1. Hyperparathyroidism.&#xD;
&#xD;
          2. Kidney stones.&#xD;
&#xD;
          3. Liver diseases.&#xD;
&#xD;
          4. Granulomatous disorders (sarcoidosis, tuberculosis)&#xD;
&#xD;
        6. Patients 17 years old and younger.&#xD;
&#xD;
        7. Use of supplements containing vitamin D at total doses higher than 1000 IU/day within 12&#xD;
        weeks of the baseline visit initiating the protocol and unwillingness to limit vitamin D&#xD;
        supplementation dosage to no higher than 1000 IU/day for the duration of the study.&#xD;
&#xD;
        8. Use of supplements containing calcium at total doses higher than 600 mg/day within 1&#xD;
        week of the baseline visit initiating the protocol and unwillingness to limit calcium&#xD;
        supplementation dosage to no more than 600 mg/day for the duration of the study.&#xD;
&#xD;
        9. History of intolerance to vitamin D supplements.&#xD;
&#xD;
        10. Women only: A. Pregnancy (past 1 year by report or positive pregnancy test at&#xD;
        screening), intent to become pregnant in the next 4 years or unprotected intercourse.&#xD;
        History of gestational diabetes is not an exclusion criterion.&#xD;
&#xD;
        B. Currently breastfeeding. C. Use of oral contraceptives or menopausal hormone therapy&#xD;
        started within 3 months of baseline. Stable regimen of oral contraceptives or any other&#xD;
        hormonal method of contraception (e.g. implantable) is allowed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <last_update_submitted>April 3, 2015</last_update_submitted>
  <last_update_submitted_qc>April 3, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 6, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>King Abdulaziz University</investigator_affiliation>
    <investigator_full_name>Siraj Omar Wali</investigator_full_name>
    <investigator_title>Assistant professor</investigator_title>
  </responsible_party>
  <keyword>Vitamin D</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psychomotor Agitation</mesh_term>
    <mesh_term>Restless Legs Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</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/NCT02256215
org study id: RLSD-1234
nct id: NCT02256215
lead sponsor: 
collaborator: 
Restless Legs Syndrome (RLS) is a sensorimotor disorder that syndrome may substantially
      interfere with normal sleep, leading to significant impairment in patients' productivity and
      quality of life.

      The most common and potent of all treatment regimens are the dopaminergic agonist agents,
      which carry serious adverse events in their prolonged use despite their augmentation. A few
      basic studies have suggested a potential relationship between vitamin D and RLS. It has been
      implicated that dopaminergic system dysfunction plays a role in the development of RLS, while
      vitamin D has a protective effect on that system. This has been further substantiated by few
      clinical observations that showed prompt improvement of RLS patients upon receiving
      dopaminergic agents such as carbamazepine. Other studies have revealed low serum levels of
      vitamin D in RLS patients, along with remarkable improvement after vitamin D replacement
      therapy, as has been demonstrated in a recent pilot study.

      This collectively points at vitamin D as a potential, more natural and safer treatment option
      for those suffering from RLS. However, the role of vitamin D in RLS has not been effectively
      investigated. The aim of this 12-week, triple-blinded, randomized, placebo-controlled trial
      is to confirm the relationship between vitamin D deficiency and RLS and hence elucidate the
      efficacy of vitamin D replacement therapy in reducing the severity of RLS, with predictions
      that the results will contribute to better understanding of the disease and its management.

      Methods and Materials: This 12-week, double-blinded, randomized, placebo-controlled trial is
      take place over a duration of 2 years. It will be held in the city of Jeddah to assess a
      sample of Saudi residents of the Western region.

      It is comprised of a number of visits, with the first one consisting of a questionnaire that
      is to be answered regarding RLS, physical examination, electromyography, the objective
      multiple Suggested Immobilization test, and blood tests. The main purpose of the second visit
      is to establish a diagnosis of RLS.

      Clinic visits number 3 through 6 comprise the pre-randomizaiton phase. Their purpose is to
      determine the patient's adherence to trial procedures and pharmacological treatment.

      Then, patients are to visit the clinic every two weeks for the first two months, then at week
      12. Patients will be assessed in regards to treatment response and adverse effects through
      history and physical examination along with further blood tests.

      Aim: to confirm the relationship between vitamin D deficiency and RLS and hence elucidate the
      efficacy of vitamin D replacement therapy in reducing the severity of RLS, with predictions
      that the results will contribute to better understanding of the disease and its management.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in The International Restless Legs Scale (IRLS) total score
time frame: 12 weeks
arm group label: Vitamin D
arm group type: Experimental
description: • All patients will have their serum vitamin D levels measured at the baseline visit. Those assigned to the treatment arm (group A) will receive either 50,000 international units of vitamin D3 by mouth once or more per week for six to eight weeks, then 800 to 1000 (or more) international units of vitamin D3 daily thereafter, this is according to the recommendations of the Endocrine Society clinical practice guideline 2011. Group B patients will receive placebo supplements identical in appearance to the vitamin D supplements.
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Vitamin D
arm group label: Vitamin D
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: King Abdulaziz University
investigator full name: Siraj Omar Wali
investigator title: Assistant professor
mesh term: Psychomotor Agitation
mesh term: Restless Legs Syndrome
mesh term: Syndrome
mesh term: Vitamin D