<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/NCT03000777</url>
  </required_header>
  <id_info>
    <org_study_id>IC/LV/MEL-ZN/SFC</org_study_id>
    <nct_id>NCT03000777</nct_id>
  </id_info>
  <brief_title>Oral Melatonin Plus Zinc Supplementation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)</brief_title>
  <acronym>MELATOZINC</acronym>
  <official_title>An Unicentric, Double-blind, Placebo Controlled, Phase IV Clinical Trial of Oral Melatonin Plus Zinc to Evaluate Relieving Self-reported Fatigue in CFS/ME</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laboratorios Viñas, S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Vall d'Hebron</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Laboratorio Echevarne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Laboratorios Viñas, S.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effects of oral melatonin plus zinc&#xD;
      supplementation in relieving self-reported fatigue in CFS/ME&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a complex medical condition,&#xD;
      characterized by severe disabling fatigue with no known cause, no established diagnostic&#xD;
      tests, and no universally effective treatment. No studies have evaluated symptomatic&#xD;
      treatment using oral melatonin plus zinc supplementation in CFS/ME. The primary endpoint was&#xD;
      to assess the effect of melatonin plus zinc supplementation on self-reported fatigue.&#xD;
      Secondary measures included self-reported outcomes of sleep problems, anxiety/depression,&#xD;
      dysautonomia, QoL and side-effects during treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2016</start_date>
  <completion_date type="Actual">September 2017</completion_date>
  <primary_completion_date type="Actual">July 2017</primary_completion_date>
  <phase>N/A</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate relieving self-reported fatigue using the Fatigue Impact Scale 40-items (FIS 40) questionnaire after oral melatonin plus zinc administration</measure>
    <time_frame>within the first 16 weeks (plus 4 weeks with no treatment)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Side effects during treatment.</measure>
    <time_frame>within the first 16 weeks (plus 4 weeks with no treatment)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported sleep quality through the Pittsburgh Sleep Quality Index (PSQI) questionnaire.</measure>
    <time_frame>within the first 16 weeks (plus 4 weeks with no treatment)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported anxiety/depression through the Hospital Anxiety and Depression Scale (HADS) questionnaire.</measure>
    <time_frame>within the first 16 weeks (plus 4 weeks with no treatment)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported dysautonomia using the Composite Autonomic Symptom Score 31-items (COMPASS 31) questionnaire.</measure>
    <time_frame>within the first 16 weeks (plus 4 weeks with no treatment)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported QoL through the Short Form Health Survey 36-items (SF-36) questionnaire.</measure>
    <time_frame>within the first 16 weeks (plus 4 weeks with no treatment)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Fatigue Syndrome, Chronic</condition>
  <condition>Myalgic Encephalomyelitis</condition>
  <arm_group>
    <arm_group_label>Melatonin plus Zinc</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Melatonin plus Zinc</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Isomaltose</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>melatonin plus zinc</intervention_name>
    <description>Melatonin 1 mg plus Zinc 10 mg o.d. 1 hour before going to bed during 16 weeks</description>
    <arm_group_label>Melatonin plus Zinc</arm_group_label>
    <other_name>MelatoZinc</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Isomaltose o.d. 1 hour before going to bed during 16 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  CFS patient based on the 1994 Centers for Disease Control and Prevention/Fukuda&#xD;
             definition.&#xD;
&#xD;
          -  Patient who provided signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are participating in another clinical trial of the same or different&#xD;
             nature previous 30 days prior to inclusion.&#xD;
&#xD;
          -  Any subject that, in the judgment of the investigator, is not able to follow the&#xD;
             instructions or to perform a good completion of the treatment.&#xD;
&#xD;
          -  Subjects that do not provide signed informed consent.&#xD;
&#xD;
          -  Patients who are receiving any of the drugs or products that may interfere with the&#xD;
             results, and whose withdrawal could be a relevant medical problem.&#xD;
&#xD;
          -  Patients receiving oral anticoagulants.&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Patients with hypersensitivity to melatonin and/or zinc.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>José Alegre, MD; PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vall d'Hebron University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vall d'Hebron University Hospital</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Castro-Marrero J, Cordero MD, Saez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. 2013 Nov 20;19(15):1855-60. doi: 10.1089/ars.2013.5346. Epub 2013 May 29.</citation>
    <PMID>23600892</PMID>
  </reference>
  <reference>
    <citation>Castro-Marrero J, Cordero MD, Segundo MJ, Saez-Francas N, Calvo N, Roman-Malo L, Aliste L, Fernandez de Sevilla T, Alegre J. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid Redox Signal. 2015 Mar 10;22(8):679-85. doi: 10.1089/ars.2014.6181. Epub 2014 Dec 18.</citation>
    <PMID>25386668</PMID>
  </reference>
  <reference>
    <citation>Castro-Marrero J, Saez-Francas N, Segundo MJ, Calvo N, Faro M, Aliste L, Fernandez de Sevilla T, Alegre J. Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomized, controlled, double-blind trial. Clin Nutr. 2016 Aug;35(4):826-34. doi: 10.1016/j.clnu.2015.07.010. Epub 2015 Jul 17.</citation>
    <PMID>26212172</PMID>
  </reference>
  <reference>
    <citation>Saez-Francas N, Calvo N, Alegre J, Castro-Marrero J, Ramirez N, Hernandez-Vara J, Casas M. Childhood trauma in Chronic Fatigue Syndrome: focus on personality disorders and psychopathology. Compr Psychiatry. 2015 Oct;62:13-9. doi: 10.1016/j.comppsych.2015.06.010. Epub 2015 Jun 17.</citation>
    <PMID>26343462</PMID>
  </reference>
  <reference>
    <citation>Faro M, Saez-Francas N, Castro-Marrero J, Aliste L, Fernandez de Sevilla T, Alegre J. Gender differences in chronic fatigue syndrome. Reumatol Clin. 2016 Mar-Apr;12(2):72-7. doi: 10.1016/j.reuma.2015.05.007. Epub 2015 Jul 17. English, Spanish.</citation>
    <PMID>26190206</PMID>
  </reference>
  <reference>
    <citation>Calvo N, Saez-Francas N, Valero S, Alegre J, Casas M. Comorbid personality disorders in chronic fatigue syndrome patients: a marker of psychopathological severity. Actas Esp Psiquiatr. 2015 Mar-Apr;43(2):58-65. Epub 2015 Mar 1.</citation>
    <PMID>25812543</PMID>
  </reference>
  <reference>
    <citation>Faro M, Alegre J. [Fibromyalgia as a comorbid phenomenon in autoinflammatory diseases]. Med Clin (Barc). 2015 Jun 8;144(11):525. doi: 10.1016/j.medcli.2014.07.033. Epub 2014 Nov 26. No abstract available. Spanish.</citation>
    <PMID>25433788</PMID>
  </reference>
  <reference>
    <citation>Santamarina-Perez P, Eiroa-Orosa FJ, Rodriguez-Urrutia A, Qureshi A, Alegre J. Neuropsychological impairment in female patients with chronic fatigue syndrome: a preliminary study. Appl Neuropsychol Adult. 2014;21(2):120-7. doi: 10.1080/09084282.2013.771264. Epub 2013 Aug 13.</citation>
    <PMID>24826505</PMID>
  </reference>
  <reference>
    <citation>Saez-Francas N, Valero S, Calvo N, Goma-I-Freixanet M, Alegre J, de Sevilla TF, Casas M. Chronic fatigue syndrome and personality: a case-control study using the Alternative Five Factor Model. Psychiatry Res. 2014 May 30;216(3):373-8. doi: 10.1016/j.psychres.2014.02.031. Epub 2014 Mar 3.</citation>
    <PMID>24630915</PMID>
  </reference>
  <reference>
    <citation>Docampo E, Escaramis G, Gratacos M, Villatoro S, Puig A, Kogevinas M, Collado A, Carbonell J, Rivera J, Vidal J, Alegre J, Estivill X, Rabionet R. Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system. Pain. 2014 Jun;155(6):1102-1109. doi: 10.1016/j.pain.2014.02.016. Epub 2014 Feb 26.</citation>
    <PMID>24582949</PMID>
  </reference>
  <reference>
    <citation>Faro M, Saez-Francas N, Castro-Marrero J, Aliste L, Collado A, Alegre J. [Impact of the fibromyalgia in the chronic fatigue syndrome]. Med Clin (Barc). 2014 Jun 16;142(12):519-25. doi: 10.1016/j.medcli.2013.06.030. Epub 2014 Jan 2. Spanish.</citation>
    <PMID>24387955</PMID>
  </reference>
  <reference>
    <citation>Blazquez A, Ruiz E, Aliste L, Garcia-Quintana A, Alegre J. The effect of fatigue and fibromyalgia on sexual dysfunction in women with chronic fatigue syndrome. J Sex Marital Ther. 2015;41(1):1-10. doi: 10.1080/0092623X.2013.864370. Epub 2014 Mar 11.</citation>
    <PMID>24274008</PMID>
  </reference>
  <reference>
    <citation>Valero S, Saez-Francas N, Calvo N, Alegre J, Casas M. The role of neuroticism, perfectionism and depression in chronic fatigue syndrome. A structural equation modeling approach. Compr Psychiatry. 2013 Oct;54(7):1061-7. doi: 10.1016/j.comppsych.2013.04.015. Epub 2013 Jun 5.</citation>
    <PMID>23759150</PMID>
  </reference>
  <reference>
    <citation>Curriu M, Carrillo J, Massanella M, Rigau J, Alegre J, Puig J, Garcia-Quintana AM, Castro-Marrero J, Negredo E, Clotet B, Cabrera C, Blanco J. Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome. J Transl Med. 2013 Mar 20;11:68. doi: 10.1186/1479-5876-11-68.</citation>
    <PMID>23514202</PMID>
  </reference>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <last_update_submitted>August 8, 2018</last_update_submitted>
  <last_update_submitted_qc>August 8, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>melatonin</keyword>
  <keyword>zinc</keyword>
  <keyword>Myalgic Encephalomyelitis</keyword>
  <keyword>Chronic Fatigue Syndrome</keyword>
  <keyword>sleep</keyword>
  <keyword>pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Encephalomyelitis</mesh_term>
    <mesh_term>Fatigue Syndrome, Chronic</mesh_term>
    <mesh_term>Myalgia</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Fatigue</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_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/NCT03000777
org study id: IC/LV/MEL-ZN/SFC
nct id: NCT03000777
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate the effects of oral melatonin plus zinc
      supplementation in relieving self-reported fatigue in CFS/ME
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a complex medical condition,
      characterized by severe disabling fatigue with no known cause, no established diagnostic
      tests, and no universally effective treatment. No studies have evaluated symptomatic
      treatment using oral melatonin plus zinc supplementation in CFS/ME. The primary endpoint was
      to assess the effect of melatonin plus zinc supplementation on self-reported fatigue.
      Secondary measures included self-reported outcomes of sleep problems, anxiety/depression,
      dysautonomia, QoL and side-effects during treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: To evaluate relieving self-reported fatigue using the Fatigue Impact Scale 40-items (FIS 40) questionnaire after oral melatonin plus zinc administration
time frame: within the first 16 weeks (plus 4 weeks with no treatment)
measure: Side effects during treatment.
time frame: within the first 16 weeks (plus 4 weeks with no treatment)
measure: Self-reported sleep quality through the Pittsburgh Sleep Quality Index (PSQI) questionnaire.
time frame: within the first 16 weeks (plus 4 weeks with no treatment)
measure: Self-reported anxiety/depression through the Hospital Anxiety and Depression Scale (HADS) questionnaire.
time frame: within the first 16 weeks (plus 4 weeks with no treatment)
measure: Self-reported dysautonomia using the Composite Autonomic Symptom Score 31-items (COMPASS 31) questionnaire.
time frame: within the first 16 weeks (plus 4 weeks with no treatment)
measure: Self-reported QoL through the Short Form Health Survey 36-items (SF-36) questionnaire.
time frame: within the first 16 weeks (plus 4 weeks with no treatment)
arm group label: Melatonin plus Zinc
arm group type: Experimental
description: Melatonin plus Zinc
arm group label: Placebo
arm group type: Placebo Comparator
description: Isomaltose
intervention type: Dietary Supplement
intervention name: melatonin plus zinc
description: Melatonin 1 mg plus Zinc 10 mg o.d. 1 hour before going to bed during 16 weeks
arm group label: Melatonin plus Zinc
other name: MelatoZinc
intervention type: Other
intervention name: Placebo
description: Isomaltose o.d. 1 hour before going to bed during 16 weeks
arm group label: Placebo
other name: Control
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: José Alegre, MD; PhD
role: Principal Investigator
affiliation: Vall d'Hebron University Hospital
facility: 
country: Spain
citation: Castro-Marrero J, Cordero MD, Saez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. 2013 Nov 20;19(15):1855-60. doi: 10.1089/ars.2013.5346. Epub 2013 May 29.
PMID: 23600892
citation: Castro-Marrero J, Cordero MD, Segundo MJ, Saez-Francas N, Calvo N, Roman-Malo L, Aliste L, Fernandez de Sevilla T, Alegre J. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid Redox Signal. 2015 Mar 10;22(8):679-85. doi: 10.1089/ars.2014.6181. Epub 2014 Dec 18.
PMID: 25386668
citation: Castro-Marrero J, Saez-Francas N, Segundo MJ, Calvo N, Faro M, Aliste L, Fernandez de Sevilla T, Alegre J. Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomized, controlled, double-blind trial. Clin Nutr. 2016 Aug;35(4):826-34. doi: 10.1016/j.clnu.2015.07.010. Epub 2015 Jul 17.
PMID: 26212172
citation: Saez-Francas N, Calvo N, Alegre J, Castro-Marrero J, Ramirez N, Hernandez-Vara J, Casas M. Childhood trauma in Chronic Fatigue Syndrome: focus on personality disorders and psychopathology. Compr Psychiatry. 2015 Oct;62:13-9. doi: 10.1016/j.comppsych.2015.06.010. Epub 2015 Jun 17.
PMID: 26343462
citation: Faro M, Saez-Francas N, Castro-Marrero J, Aliste L, Fernandez de Sevilla T, Alegre J. Gender differences in chronic fatigue syndrome. Reumatol Clin. 2016 Mar-Apr;12(2):72-7. doi: 10.1016/j.reuma.2015.05.007. Epub 2015 Jul 17. English, Spanish.
PMID: 26190206
citation: Calvo N, Saez-Francas N, Valero S, Alegre J, Casas M. Comorbid personality disorders in chronic fatigue syndrome patients: a marker of psychopathological severity. Actas Esp Psiquiatr. 2015 Mar-Apr;43(2):58-65. Epub 2015 Mar 1.
PMID: 25812543
citation: Faro M, Alegre J. [Fibromyalgia as a comorbid phenomenon in autoinflammatory diseases]. Med Clin (Barc). 2015 Jun 8;144(11):525. doi: 10.1016/j.medcli.2014.07.033. Epub 2014 Nov 26. No abstract available. Spanish.
PMID: 25433788
citation: Santamarina-Perez P, Eiroa-Orosa FJ, Rodriguez-Urrutia A, Qureshi A, Alegre J. Neuropsychological impairment in female patients with chronic fatigue syndrome: a preliminary study. Appl Neuropsychol Adult. 2014;21(2):120-7. doi: 10.1080/09084282.2013.771264. Epub 2013 Aug 13.
PMID: 24826505
citation: Saez-Francas N, Valero S, Calvo N, Goma-I-Freixanet M, Alegre J, de Sevilla TF, Casas M. Chronic fatigue syndrome and personality: a case-control study using the Alternative Five Factor Model. Psychiatry Res. 2014 May 30;216(3):373-8. doi: 10.1016/j.psychres.2014.02.031. Epub 2014 Mar 3.
PMID: 24630915
citation: Docampo E, Escaramis G, Gratacos M, Villatoro S, Puig A, Kogevinas M, Collado A, Carbonell J, Rivera J, Vidal J, Alegre J, Estivill X, Rabionet R. Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system. Pain. 2014 Jun;155(6):1102-1109. doi: 10.1016/j.pain.2014.02.016. Epub 2014 Feb 26.
PMID: 24582949
citation: Faro M, Saez-Francas N, Castro-Marrero J, Aliste L, Collado A, Alegre J. [Impact of the fibromyalgia in the chronic fatigue syndrome]. Med Clin (Barc). 2014 Jun 16;142(12):519-25. doi: 10.1016/j.medcli.2013.06.030. Epub 2014 Jan 2. Spanish.
PMID: 24387955
citation: Blazquez A, Ruiz E, Aliste L, Garcia-Quintana A, Alegre J. The effect of fatigue and fibromyalgia on sexual dysfunction in women with chronic fatigue syndrome. J Sex Marital Ther. 2015;41(1):1-10. doi: 10.1080/0092623X.2013.864370. Epub 2014 Mar 11.
PMID: 24274008
citation: Valero S, Saez-Francas N, Calvo N, Alegre J, Casas M. The role of neuroticism, perfectionism and depression in chronic fatigue syndrome. A structural equation modeling approach. Compr Psychiatry. 2013 Oct;54(7):1061-7. doi: 10.1016/j.comppsych.2013.04.015. Epub 2013 Jun 5.
PMID: 23759150
citation: Curriu M, Carrillo J, Massanella M, Rigau J, Alegre J, Puig J, Garcia-Quintana AM, Castro-Marrero J, Negredo E, Clotet B, Cabrera C, Blanco J. Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome. J Transl Med. 2013 Mar 20;11:68. doi: 10.1186/1479-5876-11-68.
PMID: 23514202
responsible party type: Sponsor
mesh term: Encephalomyelitis
mesh term: Fatigue Syndrome, Chronic
mesh term: Myalgia
mesh term: Syndrome
mesh term: Fatigue
mesh term: Melatonin
sharing ipd: No