xml: <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/NCT05970861</url>
    </required_header>
    <id_info>
      <org_study_id>KazNMU_Saumal_COVID</org_study_id>
      <nct_id>NCT05970861</nct_id>
    </id_info>
    <brief_title>Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients</brief_title>
    <official_title>Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Asfendiyarov Kazakh National Medical University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Asfendiyarov Kazakh National Medical University</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>
        The efficacy of natural foods such as freeze-dried mare's milk (Saumal) in post-COVID&#xD;
        syndrome therapy has not been studied. The literature review has shown that researchers have&#xD;
        focused more on evidence-based medications and less on natural products. Some raw foods, such&#xD;
        as freeze-dried mare's milk, contribute to forming complete immune complexes and have&#xD;
        antioxidant, membrane stabilizing, and antiviral effects.&#xD;
  &#xD;
        The use of Saumal proved its effectiveness in patients suffering from chronic hepatitis C.&#xD;
        After 4 weeks of using freeze-dried mare's milk, the biodiversity of the intestinal&#xD;
        microbiome was increased. The content of bacteria secreting short-chain fatty acids also&#xD;
        increased.&#xD;
  &#xD;
        The study aims to confirm these effects at the gene level in patients who underwent COVID-19.&#xD;
        This study will allow us to develop a highly evidence-based component of rehabilitation&#xD;
        therapy in patients after COVID-19.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study consists of three stages. Stage I. Randomized division of 76 patients under study&#xD;
        into a main group of 38 patients receiving Saumal for 4 weeks and a control group of 38&#xD;
        patients not receiving Saumal. All respondents have suffered from COVID-19 in the last 6&#xD;
        months. At the moment of the research, all patients will be staying in rehabilitation centers&#xD;
        in Almaty City.&#xD;
  &#xD;
        The study's biological material will be collected from the respondents (gut microbiome and&#xD;
        antiphospholipid antibodies).&#xD;
  &#xD;
        Stage II. The main group will be given Saumal for four weeks, after which the gut microbiome&#xD;
        and antiphospholipid antibodies will be collected from both groups once again. This will&#xD;
        allow us to assess the impact of freeze-dried mare's milk on the condition of the gut&#xD;
        microbiome and antiphospholipid antibodies.&#xD;
  &#xD;
        Stage III. Data analysis.&#xD;
  &#xD;
          1. Based on the results of gut microbiome sequencing and ELISA (antiphospholipid&#xD;
             antibodies) in the main and control groups, we determine the dynamic changes of that&#xD;
             parameters during COVID-19 rehabilitation.&#xD;
  &#xD;
          2. According to the results, the effectiveness of Saumal itself regarding these 2&#xD;
             parameters will be evaluated.&#xD;
  &#xD;
          3. Develop recommendations and an algorithm for patient management after COVID-19 to&#xD;
             prevent complications.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">January 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 1, 2023</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Gut Microbiome</measure>
      <time_frame>4 weeks</time_frame>
      <description>Intestinal microbiome studies will be performed using the Ion 16S™ Metagenomics Kit and Ion Torrent Next Generation Sequencing (NGS) technology.&#xD;
  Creation of libraries for NGS sequencing. The commercial Ion 16S™ The Metagenomics Kit includes two primer pools that can amplify the hypervariable regions of 16S rRNA in bacteria. The first pool produces V2-4-8, while the second pool allows for the production of V3-6 and 7-9 regions of 16S rRNA.Sequencing will be performed on an Ion S5 analyzer using an Ion 520 Chip Kit. Once the PCR products have been run, it is important to follow standard procedures for fragment end recovery, adaptor ligation, nick gap repair, qualitative and quantitative assessment of non-amplified libraries, and pooling.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Antiphospholipid antibodies</measure>
      <time_frame>4 weeks</time_frame>
      <description>IgG or IgM autoantibodies to cardiolipin, phosphatidyl serine, phosphatidyl-inositol, phosphatidyl acid, and β2-glycoprotein I are determined in human venous blood serum by enzyme immunoassay (ELISA) using the Anti-Phospholipid Screen IgG/IgM kit.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Immune status changes</measure>
      <time_frame>4 weeks</time_frame>
      <description>Levels of immune status markers (Immunoglobulin G, Immunoglobulin M, Immunoglobulin A) will be detected from blood samples.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">76</enrollment>
    <condition>COVID-19</condition>
    <arm_group>
      <arm_group_label>Main Group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients who had suffered from COVID-19 in the six months before the start of the study. Patients will receive Saumal (freeze-dried mare milk) for four weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control Group</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Patients who had suffered from COVID-19 in the six months before the start of the study. There will be no intervention.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Freeze-dried Mare Milk (Saumal)</intervention_name>
      <description>Freeze-dried Mare Milk (Saumal) is frequently reported for having therapeutic and dietary properties associated with specific chemical composition and certain physical properties of the product. It contains a total of about 40 biologically active components, the most important of them vitamins A, C, B1, B2, B6, and B12, amino acids, enzymes, and trace elements (low molecular weight peptides, lactalbumins, and globulins). Saumal will be administered to patients at a dose of 20 grams of dry powder per 200 ml of water, 2 times a day, 30 minutes before the meal, for 4 weeks.</description>
      <arm_group_label>Main Group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age 18 years and older;&#xD;
  &#xD;
            2. Patients in rehabilitation after COVID-19;&#xD;
  &#xD;
            3. Signed informed consent;&#xD;
  &#xD;
            4. Presence of patient's history of COVID-19, reliably established by PCR+ /presence of&#xD;
               IgG/ diagnosis of coronavirus pneumonia on Computer Tomography based on discharge from&#xD;
               hospital or outpatient records.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Chronic inflammatory bowel disease;&#xD;
  &#xD;
            2. Gut microbiota transplantation;&#xD;
  &#xD;
            3. Chronic pancreatic disease, period of exacerbation;&#xD;
  &#xD;
            4. Liver cirrhosis, Metavir stage 3-4;&#xD;
  &#xD;
            5. Any disease in the decompensation stage;&#xD;
  &#xD;
            6. Neuralgic and psychological disorders that interfere with the study;&#xD;
  &#xD;
            7. Cancer;&#xD;
  &#xD;
            8. Non-transportable patients;&#xD;
  &#xD;
            9. Patients who do not reside in Almaty;&#xD;
  &#xD;
           10. Patients who have refused to participate in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Abdugani Musayev, Ph.D., M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Asfendiyarov Kazakh National Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Abdugani Musayev, Ph.D., M.D.</last_name>
      <phone>+7 777 2509406</phone>
      <email>musaev.dr56@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Vildan Indershiyev</last_name>
      <phone>+7 707 5832221</phone>
      <email>vildanindershiyev@gmail.com</email>
    </overall_contact_backup>
    <results_reference>
      <citation>Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, Wan Y, Chung ACK, Cheung CP, Chen N, Lai CKC, Chen Z, Tso EYK, Fung KSC, Chan V, Ling L, Joynt G, Hui DSC, Chan FKL, Chan PKS, Ng SC. Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology. 2020 Sep;159(3):944-955.e8. doi: 10.1053/j.gastro.2020.05.048. Epub 2020 May 20.</citation>
      <PMID>32442562</PMID>
    </results_reference>
    <results_reference>
      <citation>Yeoh YK, Zuo T, Lui GC, Zhang F, Liu Q, Li AY, Chung AC, Cheung CP, Tso EY, Fung KS, Chan V, Ling L, Joynt G, Hui DS, Chow KM, Ng SSS, Li TC, Ng RW, Yip TC, Wong GL, Chan FK, Wong CK, Chan PK, Ng SC. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021 Apr;70(4):698-706. doi: 10.1136/gutjnl-2020-323020. Epub 2021 Jan 11.</citation>
      <PMID>33431578</PMID>
    </results_reference>
    <results_reference>
      <citation>Romaniuk K., Majszyk-Świątek M., Kryszak K., Danielewicz A., Andraszek K. Alternative use of mare milk. Folia Pomer. Univ. Technol. Stetin. 2019;348:121-130. doi: 10.21005/AAPZ2019.49.1.13.</citation>
    </results_reference>
    <results_reference>
      <citation>Kushugulova A., Kozhakhmetov S., Sattybayeva R., Nurgozhina A., Ziyat A., Yadav H., Marotta F. Mare's milk as a prospective functional product. Funct. Food Health Dis. 2018;8:537-543. doi: 10.31989/ffhd.v8i11.528.</citation>
    </results_reference>
    <results_reference>
      <citation>Musayev, A., Yeshmanova, A., Pakhomenko, Y., Kozhakhmetov, S.S., Kushugulova, A.K. Effects of Environmental Pollutants on Intestinal Microbiome Under the Influence Of Mare's Milk In Patients with Hepatitis C. Procedia Environmental Science, Engineering and Management 2020;7(4):605-611.</citation>
    </results_reference>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Asfendiyarov Kazakh National Medical University</investigator_affiliation>
      <investigator_full_name>Vildan Indershiyev</investigator_full_name>
      <investigator_title>Ph.D. candidate</investigator_title>
    </responsible_party>
    <keyword>COVID-19</keyword>
    <keyword>gut microbiome</keyword>
    <keyword>antiphospholipid antibodies</keyword>
    <keyword>rehabilitation</keyword>
    <keyword>food products</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>COVID-19</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05970861
  org study id: KazNMU_Saumal_COVID
  nct id: NCT05970861
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The efficacy of natural foods such as freeze-dried mare's milk (Saumal) in post-COVID
        syndrome therapy has not been studied. The literature review has shown that researchers have
        focused more on evidence-based medications and less on natural products. Some raw foods, such
        as freeze-dried mare's milk, contribute to forming complete immune complexes and have
        antioxidant, membrane stabilizing, and antiviral effects.
  
        The use of Saumal proved its effectiveness in patients suffering from chronic hepatitis C.
        After 4 weeks of using freeze-dried mare's milk, the biodiversity of the intestinal
        microbiome was increased. The content of bacteria secreting short-chain fatty acids also
        increased.
  
        The study aims to confirm these effects at the gene level in patients who underwent COVID-19.
        This study will allow us to develop a highly evidence-based component of rehabilitation
        therapy in patients after COVID-19.
  The study consists of three stages. Stage I. Randomized division of 76 patients under study
        into a main group of 38 patients receiving Saumal for 4 weeks and a control group of 38
        patients not receiving Saumal. All respondents have suffered from COVID-19 in the last 6
        months. At the moment of the research, all patients will be staying in rehabilitation centers
        in Almaty City.
  
        The study's biological material will be collected from the respondents (gut microbiome and
        antiphospholipid antibodies).
  
        Stage II. The main group will be given Saumal for four weeks, after which the gut microbiome
        and antiphospholipid antibodies will be collected from both groups once again. This will
        allow us to assess the impact of freeze-dried mare's milk on the condition of the gut
        microbiome and antiphospholipid antibodies.
  
        Stage III. Data analysis.
  
          1. Based on the results of gut microbiome sequencing and ELISA (antiphospholipid
             antibodies) in the main and control groups, we determine the dynamic changes of that
             parameters during COVID-19 rehabilitation.
  
          2. According to the results, the effectiveness of Saumal itself regarding these 2
             parameters will be evaluated.
  
          3. Develop recommendations and an algorithm for patient management after COVID-19 to
             prevent complications.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Gut Microbiome
  time frame: 4 weeks
  description: Intestinal microbiome studies will be performed using the Ion 16S™ Metagenomics Kit and Ion Torrent Next Generation Sequencing (NGS) technology.
  Creation of libraries for NGS sequencing. The commercial Ion 16S™ The Metagenomics Kit includes two primer pools that can amplify the hypervariable regions of 16S rRNA in bacteria. The first pool produces V2-4-8, while the second pool allows for the production of V3-6 and 7-9 regions of 16S rRNA.Sequencing will be performed on an Ion S5 analyzer using an Ion 520 Chip Kit. Once the PCR products have been run, it is important to follow standard procedures for fragment end recovery, adaptor ligation, nick gap repair, qualitative and quantitative assessment of non-amplified libraries, and pooling.
  measure: Antiphospholipid antibodies
  time frame: 4 weeks
  description: IgG or IgM autoantibodies to cardiolipin, phosphatidyl serine, phosphatidyl-inositol, phosphatidyl acid, and β2-glycoprotein I are determined in human venous blood serum by enzyme immunoassay (ELISA) using the Anti-Phospholipid Screen IgG/IgM kit.
  measure: Immune status changes
  time frame: 4 weeks
  description: Levels of immune status markers (Immunoglobulin G, Immunoglobulin M, Immunoglobulin A) will be detected from blood samples.
  arm group label: Main Group
  arm group type: Experimental
  description: Patients who had suffered from COVID-19 in the six months before the start of the study. Patients will receive Saumal (freeze-dried mare milk) for four weeks.
  arm group label: Control Group
  arm group type: No Intervention
  description: Patients who had suffered from COVID-19 in the six months before the start of the study. There will be no intervention.
  intervention type: Dietary Supplement
  intervention name: Freeze-dried Mare Milk (Saumal)
  description: Freeze-dried Mare Milk (Saumal) is frequently reported for having therapeutic and dietary properties associated with specific chemical composition and certain physical properties of the product. It contains a total of about 40 biologically active components, the most important of them vitamins A, C, B1, B2, B6, and B12, amino acids, enzymes, and trace elements (low molecular weight peptides, lactalbumins, and globulins). Saumal will be administered to patients at a dose of 20 grams of dry powder per 200 ml of water, 2 times a day, 30 minutes before the meal, for 4 weeks.
  arm group label: Main Group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Abdugani Musayev, Ph.D., M.D.
  role: Principal Investigator
  affiliation: Asfendiyarov Kazakh National Medical University
  last name: Abdugani Musayev, Ph.D., M.D.
  phone: +7 777 2509406
  email: musaev.dr56@gmail.com
  last name: Vildan Indershiyev
  phone: +7 707 5832221
  email: vildanindershiyev@gmail.com
  citation: Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, Wan Y, Chung ACK, Cheung CP, Chen N, Lai CKC, Chen Z, Tso EYK, Fung KSC, Chan V, Ling L, Joynt G, Hui DSC, Chan FKL, Chan PKS, Ng SC. Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology. 2020 Sep;159(3):944-955.e8. doi: 10.1053/j.gastro.2020.05.048. Epub 2020 May 20.
  PMID: 32442562
  citation: Yeoh YK, Zuo T, Lui GC, Zhang F, Liu Q, Li AY, Chung AC, Cheung CP, Tso EY, Fung KS, Chan V, Ling L, Joynt G, Hui DS, Chow KM, Ng SSS, Li TC, Ng RW, Yip TC, Wong GL, Chan FK, Wong CK, Chan PK, Ng SC. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021 Apr;70(4):698-706. doi: 10.1136/gutjnl-2020-323020. Epub 2021 Jan 11.
  PMID: 33431578
  citation: Romaniuk K., Majszyk-Świątek M., Kryszak K., Danielewicz A., Andraszek K. Alternative use of mare milk. Folia Pomer. Univ. Technol. Stetin. 2019;348:121-130. doi: 10.21005/AAPZ2019.49.1.13.
  citation: Kushugulova A., Kozhakhmetov S., Sattybayeva R., Nurgozhina A., Ziyat A., Yadav H., Marotta F. Mare's milk as a prospective functional product. Funct. Food Health Dis. 2018;8:537-543. doi: 10.31989/ffhd.v8i11.528.
  citation: Musayev, A., Yeshmanova, A., Pakhomenko, Y., Kozhakhmetov, S.S., Kushugulova, A.K. Effects of Environmental Pollutants on Intestinal Microbiome Under the Influence Of Mare's Milk In Patients with Hepatitis C. Procedia Environmental Science, Engineering and Management 2020;7(4):605-611.
  responsible party type: Principal Investigator
  investigator affiliation: Asfendiyarov Kazakh National Medical University
  investigator full name: Vildan Indershiyev
  investigator title: Ph.D. candidate
  mesh term: COVID-19