<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/NCT04494204</url>
  </required_header>
  <id_info>
    <org_study_id>MGCTS/20/105</org_study_id>
    <nct_id>NCT04494204</nct_id>
  </id_info>
  <brief_title>Effect of a Combination of Treatment of Reginmune Capsule and Immunofree Tablets in the Treatment of Mild to Moderate COVID-19 Patients</brief_title>
  <official_title>An Open Label, Multicenter, Randomized, Controlled, Clinical Study to Evaluate the Efficacy and Safety of a Combination of Treatment of Reginmune Capsule and Immunofree Tablets Compared With Standard Treatment Protocol in the Treatment of Mild to Moderate COVID-19 Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PUNEET MITTAL</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nutrin GmbH</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      While novel drug discovery and vaccine studies are time taking process, re-purposing old&#xD;
      drugs against the COVID-2019 epidemic can help identify treatments, with known pre-clinical,&#xD;
      pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4&#xD;
      or can be used directly in clinical settings. Immunofree has many of the herbs which have&#xD;
      been evaluated by other trials published for Covid-19 treatment.&#xD;
&#xD;
      The Immunofree tablet of the test product is an Ayurvedic proprietary medicine and is a&#xD;
      combination of polyherbal mixture. The components of this formulation are known for their&#xD;
      anti-viral and immunomodulatory effects. Also, Reginmune, owing to its immunomodulatory&#xD;
      effect might help in easing the symptoms and decrease the viral load.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The symptoms of COVID-19 are mainly for respiratory disorders and similar to severe acute&#xD;
      respiratory symptoms. The common signs of infection observed in COVID-19 patients include&#xD;
      respiratory symptoms, sneezing, fever, cough, shortness of breath and other breathing&#xD;
      difficulties. In case of severely infected patients, infection can cause pneumonia, severe&#xD;
      acute respiratory syndrome (SARS), kidney failure and even death in many cases. There are&#xD;
      many people who had high viral load but do not develop COVID-19 symptoms like coughing or&#xD;
      sneezing. Such asymptomatic people serve as hidden carriers of virus and may further&#xD;
      contribute in enhanced transmission of virus to other people. In absence of any emergency&#xD;
      medicine or complete therapy for COVID-19; the prevention of spread of SARS-CoV2 virus and&#xD;
      regulation of infection is the prime step in controlling this epidemic disease, in which the&#xD;
      test products can be of immense value.&#xD;
&#xD;
      The test product, Capsule Reginmune is a combination of some phytochemicals, amino acids,&#xD;
      vitamins and minerals and a bio-polymer in cellular matrix. The components and their&#xD;
      pharmacological activities are as follow:&#xD;
&#xD;
      Echinacea is one of the more popular herbal supplements suggested for boosting immunity. Some&#xD;
      respiratory and antiviral research has also been done on Echinacea. Echinacea is not&#xD;
      mentioned by the Indian and Chinese Governments however in their guidelines for boosting&#xD;
      immunity.&#xD;
&#xD;
      Cats Claw (Uncaria Tomentosa)has shown potent anti-viral and immunomodulatory activity in a&#xD;
      recent study. The results demonstrated an in vitro inhibitory activity by both extract and&#xD;
      alkaloidal fraction, reducing DENV-Ag+ cell rates in treated monocytes. A multiple microbead&#xD;
      immunoassay was applied for cytokine determination (TNF-alpha, IFN-alpha, IL-6 and IL-10) in&#xD;
      infected monocyte culture supernatants. The alkaloidal fraction induced a strong&#xD;
      immunomodulation: TNF-alpha and IFN-alpha levels were significantly decreased and there was a&#xD;
      tendency towards IL-10 modulation. The researchers conclude that the alkaloidal fraction was&#xD;
      the most effective in reducing monocyte infection rates and cytokine levels. The antiviral&#xD;
      and immunomodulating in vitro effects from U. tomentosa pentacyclic oxindole alkaloids&#xD;
      displayed novel properties regarding therapeutic procedures in Dengue Fever and might be&#xD;
      further investigated as a promising candidate for clinical application.&#xD;
&#xD;
      Vitamin C: Well accepted to increase immunity and an effective antiviral. However, not many&#xD;
      people realize the vast difference in food derived vitamin C and ascorbic acid which is a&#xD;
      dead synthesized molecule used to clean pools. Therefore, it is strongly recommended that one&#xD;
      should only take food derived Vitamin C.&#xD;
&#xD;
      Zinc: There is some evidence suggesting Zinc can shorten duration of the common cold and one&#xD;
      study done in 2010 showing that Zinc had an effect on the older versions of Corona virus. An&#xD;
      abundance of evidence has accumulated over the past 50 years to demonstrate the antiviral&#xD;
      activity of zinc against a variety of viruses, and via numerous mechanisms. Clinical trial&#xD;
      data support the value of zinc in reducing the duration and severity of symptoms of the&#xD;
      common cold when administered within 24 hours of the onset of common cold symptoms. However,&#xD;
      one must be careful as not all zinc is equally bioavailable and more than 150 mg of Zinc can&#xD;
      lead to toxicity.&#xD;
&#xD;
      Copper: A study suggested that copper deficiency may lead to reduction in the number of T&#xD;
      cell lymphocytes and impaired host defense against infectious organisms.&#xD;
&#xD;
      L- Lysine: Studies shows L-Lysine supplements may help to boost immunity against certain&#xD;
      viral infections.&#xD;
&#xD;
      Aloe Vera: Numerous studies for influenza and herpes has shown that Aloe polysaccharides&#xD;
      (APS) extracted from Aloe vera leaves have evident effects on the therapy of virus infection.&#xD;
&#xD;
      Lglutamine: Glutamine is the most abundant and versatile amino acid in the body. Glutamine is&#xD;
      currently part of clinical nutritional supplementation protocols and/or recommended for&#xD;
      immune suppressed individuals.&#xD;
&#xD;
      L Arginine: Studies have shown that arginine suppressed the growth of HSV-1, concentration&#xD;
      dependently and it can boost the activity of T-cells.&#xD;
&#xD;
      L Isoleucine : It has shown to be effective against rotavirus infection. Magnesium Gluconate:&#xD;
      It has shown some immunomodulatory effects which was measured by Natural Killer cells&#xD;
      activities and phagocytosis.&#xD;
&#xD;
      Sodium Hyaluronate: Hyaluronic acid (HA), one of the main components of extra-cellular matrix&#xD;
      and most notably of the fundamental substance of conjunctive tissues, is not an inert&#xD;
      structure. Conversely, it displays important biological properties and plays a significant&#xD;
      role in crucial physiological processes especially when cellular plasticity is involved such&#xD;
      as inflammation, immune reactions, angiogenesis and would healing. It is also strongly&#xD;
      involved in neoplastic cells migration and therefore in metastatic spreading of malignant&#xD;
      tumors.&#xD;
&#xD;
      The Immunofree tablet of the test product is an Ayurvedic proprietary medicine and is a&#xD;
      combination of polyherbal mixture. The components of this formulation are known for their&#xD;
      anti-viral and immunomodulatory effects.&#xD;
&#xD;
      Kalmegh also known as Andrographis paniculata has been used in Ayurveda and other herbal&#xD;
      traditions for boosting up the immune system. It is believed that the herb has potential&#xD;
      antiviral and immunomodulatory properties owing to it containing andrographolide. The&#xD;
      following studies are done on it which suggest potential benefit.&#xD;
&#xD;
      Bhumyamalaki: It is also known as Phyllanthus niruri. It seems to exhibit anti-viral&#xD;
      anti-inflammatory activity. The following studies for SARS suggest that this may be of&#xD;
      benefit.&#xD;
&#xD;
      Glycyrrhiza glabra is also known as licorice, mulethi, etc. It has been used in TCM, Ayurveda&#xD;
      and other herbal traditions for lung health and stomach health. It is very alkalizing. It is&#xD;
      believed that it has strong antiviral properties and hence this herb is in both Chinese and&#xD;
      Indian recommendations. This herb contains glycyrrhizin which showed remarkable qualities in&#xD;
      SARS research.&#xD;
&#xD;
      Some reports suggest that strong extracts of this herb are central to the Chinese strategy in&#xD;
      Wuhan. The following studies are done on it, which suggest potential benefit.&#xD;
&#xD;
      Tulsi is also known as Ocimum sanctum has been used traditionally in India. It is considered&#xD;
      a sacred herb in Ayurveda.Following studies are done on it which suggest potential benefit.&#xD;
&#xD;
      Giloy is also known as Tinospora cordifolia has been used traditionally in Ayurveda as it&#xD;
      helps in boosting gut immunity.&#xD;
&#xD;
      Pushkarmool: It is also known as Inula racemosa and it may be an effective herb for flu&#xD;
      symptoms. It also supports the normal functioning of the respiratory system.&#xD;
&#xD;
      The drug Pushkarmool has been used in the indigenous system of medicine for a long time.&#xD;
      Pushkarmool has been reported in the texts of Ayurveda as possessing Tikta, Katu and Ushna&#xD;
      Virya and beneficial for the diseases of heart, throat. It is known to act as an expectorant.&#xD;
      It is also used in Ayurveda as an expectorant and resolvent in indurations. Its&#xD;
      pharmacological activities include cardioprotective activity, antiallergic activity,&#xD;
      antimutagenic and antiapoptotic effects, anti-inflammatory &amp; analgesic effect, adrenergic&#xD;
      beta blocking activity.&#xD;
&#xD;
      Alpinia galanga is also known as rasna, sugandhimool, etc. It has been used inTCM, Ayurveda&#xD;
      and other herbal traditions for lung health and the potential to reduce the inflammatory&#xD;
      process. It is believed that the herb has antiviral activity in human respiratory syncytial&#xD;
      viruses. The following studies are done on it which suggest potential benefit.&#xD;
&#xD;
      Draksha: It is also known as Vitis Vinifera. Studies suggeset that the herb possesses a broad&#xD;
      spectrum of pharmacological and therapeutic effects such as antioxidative, anti-inflammatory,&#xD;
      and antimicrobial activities.&#xD;
&#xD;
      Haldi is also known as Turmeric, Curcuma longa, etc. Alkaloids derived from turmeric have&#xD;
      shown potentially strong inhibitory effects on the neuraminidases from two influenza viral&#xD;
      strains. The following studies are done on it which suggest potential benefit.&#xD;
&#xD;
      Haritaki is also known as Terminalia chebula has been used in TCM, Ayurveda, and other herbal&#xD;
      traditions for boosting immunity. The herb is also possibly useful for easing the symptoms&#xD;
      associated with respiratory illnesses. The following studies are done on it which suggest&#xD;
      potential benefit.&#xD;
&#xD;
      Aloe Vera: Studies show that extracts of Aloe Vera may help to inhibit the activity of the&#xD;
      virus and support the functioning of the lungs.&#xD;
&#xD;
      Shilajit: It is also known as Asphaltum: It has been used traditionally by the Indian&#xD;
      Ayurvedic and Siddha systems of traditional medicine to enhance the quality of life. Studies&#xD;
      show that the minerals in Shilajit may also possesses immune boosting activities.&#xD;
&#xD;
      Pippali: It is also known as Piper longum. It has been used traditionally in the Ayurvedic&#xD;
      system for lung health. Studies suggest that it may help to improve lung function.&#xD;
&#xD;
      Shaival: It is also known as Asthaxantin. Studies show that it may possess antimicrobial and&#xD;
      anti-inflammatory properties.&#xD;
&#xD;
      Damanaka - Also known as Artemisia, has potential anti-malarial properties.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 7, 2020</start_date>
  <completion_date type="Actual">December 20, 2020</completion_date>
  <primary_completion_date type="Actual">December 1, 2020</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>
    <intervention_model_description>After obtaining the informed consent, patients will be screened by undergoing various assessments and after confirming eligibility, eligible patients will be randomized in the study and assigned either to the test group or control group with Best standard of care as per institutional practice, for 10 days treatment period. Patient will be hospitalized during the treatment period.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time (Days) to clinical improvement from study enrollment</measure>
    <time_frame>Day 0 - Day 10</time_frame>
    <description>This includes overall time it takes for negative covid-19 results, improvement based on a customized questionnaire for fever, cough, body ache, loss of taste or smell, or other similar conditions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants in each group with oxygen saturation more than 94% on room air for more than 24h</measure>
    <time_frame>Day 0, Day 5±1 and Day of discharge i.e Day 10±1</time_frame>
    <description>Being an important part, each patient has to be monitored for oxygen saturation level, and this would help us analyze when a subject enters from Mild to moderate stage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Value of coagulation indicators</measure>
    <time_frame>Day 0, Day 5±1 and Day of discharge i.e Day 10±1</time_frame>
    <description>D Dimer levels has to be measured to study the D dimer levels of the patient as most researchers claiming covid-19 to be relative to coagulation. This study will help us identity the same.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first negative SARS-CoV-2 PCR in NP swab</measure>
    <time_frame>Day 0, Day 5±1 and Day of discharge i.e Day 10±1</time_frame>
    <description>via ICMR recognized RT-PCR to identify when a patient is coronavirusfree</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of oxygen therapy</measure>
    <time_frame>upto day 10+1</time_frame>
    <description>To identify how long a patient needs oxygen therapy in certain case</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants in each group with need for mechanical ventilation</measure>
    <time_frame>upto day 10+1</time_frame>
    <description>This is considered as a part of pharmacovigilance, as how many people enters moderate to severe case, if any</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospitalization</measure>
    <time_frame>upto day 10+1</time_frame>
    <description>most mild cases that becomes asymptomatic are sent back from hospital and treated at home quarantine. this is to identify when a patient becomes asymptomatic</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Treatment of Covid-19 Virus Infection</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 tablets Immunofree 500 mg tablets thrice a day for 10 days and 1 capsule Reginmune 750 mg twice a day for 10 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparator Agent</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>As per standard National Clinical Management Protocol for COVID-19 by Government of India, Ministry of Health and Family Welfare, Directorate General of Health Services, (EMR Division), Version 3, 13.06.20</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Immunofree tablets and Reginmune capsule</intervention_name>
    <description>2 Immunofree tablets thrice a day at an interval of 4-5 hours for 10 days and 1 Reginmune capsule twice a day for 10 days</description>
    <arm_group_label>Comparator Agent</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Gender: Either male or non-pregnant, non-lactating female aged &gt; 18-70&#xD;
&#xD;
          -  Patients with RT-PCR confirmed diagnosis of COVID-19&#xD;
&#xD;
          -  Patients with mild to moderate COVID-19 infection having either one of the following&#xD;
             criteria: oPaO2/FiO2:200-300 OR Respiratory rate ? 24/min and SaO2/SpO2 &gt; 90% on room&#xD;
             air&#xD;
&#xD;
          -  Subjects willing to give written informed consent&#xD;
&#xD;
          -  Subjects able to take the drug orally and comply with the study protocol&#xD;
&#xD;
          -  Women of child bearing potential must have a negative urine pregnancy test prior to&#xD;
             study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with persistent vomiting&#xD;
&#xD;
          -  Critically ill patients&#xD;
&#xD;
          -  P/F ratio less than 200 (moderate-severe ARDS)&#xD;
&#xD;
          -  Shock (Requiring Vasopressor to maintain a MAP more than 65 mm of hg or MAP below 65)&#xD;
&#xD;
          -  Patients with known active hepatitis, tuberculosis and definite bacterial or fungal&#xD;
             infections&#xD;
&#xD;
          -  Patients with altered mental state&#xD;
&#xD;
          -  Patients with multiple organ failure requiring ICU monitoring and treatment&#xD;
&#xD;
          -  Patients with respiratory failure and requiring mechanical ventilation&#xD;
&#xD;
          -  Patients with any concurrent medical condition or uncontrolled, clinically significant&#xD;
             systemic disease (e.g. heart failure, hypertension, liver disease, diabetes, anemia&#xD;
             etc.) that, in the opinion of investigator precludes the subject's participation in&#xD;
             the study or interferes with the interpretation of the study results.&#xD;
&#xD;
          -  Patients with history of serology tests positive for hepatitis B, hepatitis C, or&#xD;
             human immunodeficiency virus.&#xD;
&#xD;
          -  Patients who have received specific antiviral drugs ritonavir/lopinavir, or&#xD;
             chloroquine, hydroxychloroquine, azithromycin, monoclonal antibodies within 1 week&#xD;
             before admission&#xD;
&#xD;
          -  Patient who have participated in another investigational study within 3 months prior&#xD;
             to enrollment in this study&#xD;
&#xD;
          -  Investigators, study personnel, sponsor's representatives and their first-degree&#xD;
             relatives.&#xD;
&#xD;
          -  Pregnant subjects&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Abhijit Munshi</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mittal Global Clinical Trial Services</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vijaykumar Kamat</last_name>
    <role>Study Director</role>
    <affiliation>Corival Lifesciences Pvt Ltd</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Apurve Mehra</last_name>
    <role>Study Director</role>
    <affiliation>Biogetica</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Govt Medical College and Govt General Hospital (Old RIMSGGH)</name>
      <address>
        <city>Srikakulam</city>
        <state>Andhra Pradesh</state>
        <zip>532001</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parul Institute of Ayurveda and Research Parul University</name>
      <address>
        <city>Vadodara</city>
        <state>Gujrat</state>
        <zip>391760</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lokmanya Hospital</name>
      <address>
        <city>Pune</city>
        <state>Maharashtra</state>
        <zip>411033</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <link>
    <url>https://immunofree.me/</url>
    <description>product in intervention that seeks this re-purpose study</description>
  </link>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>December 19, 2020</last_update_submitted>
  <last_update_submitted_qc>December 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Nutrin GmbH</investigator_affiliation>
    <investigator_full_name>PUNEET MITTAL</investigator_full_name>
    <investigator_title>Clinical Research Consultant</investigator_title>
  </responsible_party>
  <keyword>coronavirus</keyword>
  <keyword>covid-19</keyword>
  <keyword>covid</keyword>
  <keyword>corona</keyword>
  <keyword>coagulation</keyword>
  <keyword>immunofree</keyword>
  <keyword>mgcts</keyword>
  <keyword>biogetica</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>The trial is meant for pandemic, and any data is fruitful to the society will be shared with researchers only, without compromising personal data of the participant.</ipd_description>
  </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/NCT04494204
org study id: MGCTS/20/105
nct id: NCT04494204
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
While novel drug discovery and vaccine studies are time taking process, re-purposing old
      drugs against the COVID-2019 epidemic can help identify treatments, with known pre-clinical,
      pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4
      or can be used directly in clinical settings. Immunofree has many of the herbs which have
      been evaluated by other trials published for Covid-19 treatment.

      The Immunofree tablet of the test product is an Ayurvedic proprietary medicine and is a
      combination of polyherbal mixture. The components of this formulation are known for their
      anti-viral and immunomodulatory effects. Also, Reginmune, owing to its immunomodulatory
      effect might help in easing the symptoms and decrease the viral load.
The symptoms of COVID-19 are mainly for respiratory disorders and similar to severe acute
      respiratory symptoms. The common signs of infection observed in COVID-19 patients include
      respiratory symptoms, sneezing, fever, cough, shortness of breath and other breathing
      difficulties. In case of severely infected patients, infection can cause pneumonia, severe
      acute respiratory syndrome (SARS), kidney failure and even death in many cases. There are
      many people who had high viral load but do not develop COVID-19 symptoms like coughing or
      sneezing. Such asymptomatic people serve as hidden carriers of virus and may further
      contribute in enhanced transmission of virus to other people. In absence of any emergency
      medicine or complete therapy for COVID-19; the prevention of spread of SARS-CoV2 virus and
      regulation of infection is the prime step in controlling this epidemic disease, in which the
      test products can be of immense value.

      The test product, Capsule Reginmune is a combination of some phytochemicals, amino acids,
      vitamins and minerals and a bio-polymer in cellular matrix. The components and their
      pharmacological activities are as follow:

      Echinacea is one of the more popular herbal supplements suggested for boosting immunity. Some
      respiratory and antiviral research has also been done on Echinacea. Echinacea is not
      mentioned by the Indian and Chinese Governments however in their guidelines for boosting
      immunity.

      Cats Claw (Uncaria Tomentosa)has shown potent anti-viral and immunomodulatory activity in a
      recent study. The results demonstrated an in vitro inhibitory activity by both extract and
      alkaloidal fraction, reducing DENV-Ag+ cell rates in treated monocytes. A multiple microbead
      immunoassay was applied for cytokine determination (TNF-alpha, IFN-alpha, IL-6 and IL-10) in
      infected monocyte culture supernatants. The alkaloidal fraction induced a strong
      immunomodulation: TNF-alpha and IFN-alpha levels were significantly decreased and there was a
      tendency towards IL-10 modulation. The researchers conclude that the alkaloidal fraction was
      the most effective in reducing monocyte infection rates and cytokine levels. The antiviral
      and immunomodulating in vitro effects from U. tomentosa pentacyclic oxindole alkaloids
      displayed novel properties regarding therapeutic procedures in Dengue Fever and might be
      further investigated as a promising candidate for clinical application.

      Vitamin C: Well accepted to increase immunity and an effective antiviral. However, not many
      people realize the vast difference in food derived vitamin C and ascorbic acid which is a
      dead synthesized molecule used to clean pools. Therefore, it is strongly recommended that one
      should only take food derived Vitamin C.

      Zinc: There is some evidence suggesting Zinc can shorten duration of the common cold and one
      study done in 2010 showing that Zinc had an effect on the older versions of Corona virus. An
      abundance of evidence has accumulated over the past 50 years to demonstrate the antiviral
      activity of zinc against a variety of viruses, and via numerous mechanisms. Clinical trial
      data support the value of zinc in reducing the duration and severity of symptoms of the
      common cold when administered within 24 hours of the onset of common cold symptoms. However,
      one must be careful as not all zinc is equally bioavailable and more than 150 mg of Zinc can
      lead to toxicity.

      Copper: A study suggested that copper deficiency may lead to reduction in the number of T
      cell lymphocytes and impaired host defense against infectious organisms.

      L- Lysine: Studies shows L-Lysine supplements may help to boost immunity against certain
      viral infections.

      Aloe Vera: Numerous studies for influenza and herpes has shown that Aloe polysaccharides
      (APS) extracted from Aloe vera leaves have evident effects on the therapy of virus infection.

      Lglutamine: Glutamine is the most abundant and versatile amino acid in the body. Glutamine is
      currently part of clinical nutritional supplementation protocols and/or recommended for
      immune suppressed individuals.

      L Arginine: Studies have shown that arginine suppressed the growth of HSV-1, concentration
      dependently and it can boost the activity of T-cells.

      L Isoleucine : It has shown to be effective against rotavirus infection. Magnesium Gluconate:
      It has shown some immunomodulatory effects which was measured by Natural Killer cells
      activities and phagocytosis.

      Sodium Hyaluronate: Hyaluronic acid (HA), one of the main components of extra-cellular matrix
      and most notably of the fundamental substance of conjunctive tissues, is not an inert
      structure. Conversely, it displays important biological properties and plays a significant
      role in crucial physiological processes especially when cellular plasticity is involved such
      as inflammation, immune reactions, angiogenesis and would healing. It is also strongly
      involved in neoplastic cells migration and therefore in metastatic spreading of malignant
      tumors.

      The Immunofree tablet of the test product is an Ayurvedic proprietary medicine and is a
      combination of polyherbal mixture. The components of this formulation are known for their
      anti-viral and immunomodulatory effects.

      Kalmegh also known as Andrographis paniculata has been used in Ayurveda and other herbal
      traditions for boosting up the immune system. It is believed that the herb has potential
      antiviral and immunomodulatory properties owing to it containing andrographolide. The
      following studies are done on it which suggest potential benefit.

      Bhumyamalaki: It is also known as Phyllanthus niruri. It seems to exhibit anti-viral
      anti-inflammatory activity. The following studies for SARS suggest that this may be of
      benefit.

      Glycyrrhiza glabra is also known as licorice, mulethi, etc. It has been used in TCM, Ayurveda
      and other herbal traditions for lung health and stomach health. It is very alkalizing. It is
      believed that it has strong antiviral properties and hence this herb is in both Chinese and
      Indian recommendations. This herb contains glycyrrhizin which showed remarkable qualities in
      SARS research.

      Some reports suggest that strong extracts of this herb are central to the Chinese strategy in
      Wuhan. The following studies are done on it, which suggest potential benefit.

      Tulsi is also known as Ocimum sanctum has been used traditionally in India. It is considered
      a sacred herb in Ayurveda.Following studies are done on it which suggest potential benefit.

      Giloy is also known as Tinospora cordifolia has been used traditionally in Ayurveda as it
      helps in boosting gut immunity.

      Pushkarmool: It is also known as Inula racemosa and it may be an effective herb for flu
      symptoms. It also supports the normal functioning of the respiratory system.

      The drug Pushkarmool has been used in the indigenous system of medicine for a long time.
      Pushkarmool has been reported in the texts of Ayurveda as possessing Tikta, Katu and Ushna
      Virya and beneficial for the diseases of heart, throat. It is known to act as an expectorant.
      It is also used in Ayurveda as an expectorant and resolvent in indurations. Its
      pharmacological activities include cardioprotective activity, antiallergic activity,
      antimutagenic and antiapoptotic effects, anti-inflammatory & analgesic effect, adrenergic
      beta blocking activity.

      Alpinia galanga is also known as rasna, sugandhimool, etc. It has been used inTCM, Ayurveda
      and other herbal traditions for lung health and the potential to reduce the inflammatory
      process. It is believed that the herb has antiviral activity in human respiratory syncytial
      viruses. The following studies are done on it which suggest potential benefit.

      Draksha: It is also known as Vitis Vinifera. Studies suggeset that the herb possesses a broad
      spectrum of pharmacological and therapeutic effects such as antioxidative, anti-inflammatory,
      and antimicrobial activities.

      Haldi is also known as Turmeric, Curcuma longa, etc. Alkaloids derived from turmeric have
      shown potentially strong inhibitory effects on the neuraminidases from two influenza viral
      strains. The following studies are done on it which suggest potential benefit.

      Haritaki is also known as Terminalia chebula has been used in TCM, Ayurveda, and other herbal
      traditions for boosting immunity. The herb is also possibly useful for easing the symptoms
      associated with respiratory illnesses. The following studies are done on it which suggest
      potential benefit.

      Aloe Vera: Studies show that extracts of Aloe Vera may help to inhibit the activity of the
      virus and support the functioning of the lungs.

      Shilajit: It is also known as Asphaltum: It has been used traditionally by the Indian
      Ayurvedic and Siddha systems of traditional medicine to enhance the quality of life. Studies
      show that the minerals in Shilajit may also possesses immune boosting activities.

      Pippali: It is also known as Piper longum. It has been used traditionally in the Ayurvedic
      system for lung health. Studies suggest that it may help to improve lung function.

      Shaival: It is also known as Asthaxantin. Studies show that it may possess antimicrobial and
      anti-inflammatory properties.

      Damanaka - Also known as Artemisia, has potential anti-malarial properties.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: After obtaining the informed consent, patients will be screened by undergoing various assessments and after confirming eligibility, eligible patients will be randomized in the study and assigned either to the test group or control group with Best standard of care as per institutional practice, for 10 days treatment period. Patient will be hospitalized during the treatment period.
primary purpose: Treatment
masking: None (Open Label)
measure: Time (Days) to clinical improvement from study enrollment
time frame: Day 0 - Day 10
description: This includes overall time it takes for negative covid-19 results, improvement based on a customized questionnaire for fever, cough, body ache, loss of taste or smell, or other similar conditions
measure: Proportion of participants in each group with oxygen saturation more than 94% on room air for more than 24h
time frame: Day 0, Day 5±1 and Day of discharge i.e Day 10±1
description: Being an important part, each patient has to be monitored for oxygen saturation level, and this would help us analyze when a subject enters from Mild to moderate stage
measure: Value of coagulation indicators
time frame: Day 0, Day 5±1 and Day of discharge i.e Day 10±1
description: D Dimer levels has to be measured to study the D dimer levels of the patient as most researchers claiming covid-19 to be relative to coagulation. This study will help us identity the same.
measure: Time to first negative SARS-CoV-2 PCR in NP swab
time frame: Day 0, Day 5±1 and Day of discharge i.e Day 10±1
description: via ICMR recognized RT-PCR to identify when a patient is coronavirusfree
measure: Duration of oxygen therapy
time frame: upto day 10+1
description: To identify how long a patient needs oxygen therapy in certain case
measure: Proportion of participants in each group with need for mechanical ventilation
time frame: upto day 10+1
description: This is considered as a part of pharmacovigilance, as how many people enters moderate to severe case, if any
measure: Duration of hospitalization
time frame: upto day 10+1
description: most mild cases that becomes asymptomatic are sent back from hospital and treated at home quarantine. this is to identify when a patient becomes asymptomatic
arm group label: Intervention
arm group type: Experimental
description: 2 tablets Immunofree 500 mg tablets thrice a day for 10 days and 1 capsule Reginmune 750 mg twice a day for 10 days
arm group label: Comparator Agent
arm group type: Active Comparator
description: As per standard National Clinical Management Protocol for COVID-19 by Government of India, Ministry of Health and Family Welfare, Directorate General of Health Services, (EMR Division), Version 3, 13.06.20
intervention type: Combination Product
intervention name: Immunofree tablets and Reginmune capsule
description: 2 Immunofree tablets thrice a day at an interval of 4-5 hours for 10 days and 1 Reginmune capsule twice a day for 10 days
arm group label: Comparator Agent
arm group label: Intervention
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Abhijit Munshi
role: Principal Investigator
affiliation: Mittal Global Clinical Trial Services
last name: Vijaykumar Kamat
role: Study Director
affiliation: Corival Lifesciences Pvt Ltd
last name: Apurve Mehra
role: Study Director
affiliation: Biogetica
facility: 
facility: 
facility: 
country: India
url: https://immunofree.me/
description: product in intervention that seeks this re-purpose study
responsible party type: Sponsor-Investigator
investigator affiliation: Nutrin GmbH
investigator full name: PUNEET MITTAL
investigator title: Clinical Research Consultant
mesh term: COVID-19
sharing ipd: Undecided
ipd description: The trial is meant for pandemic, and any data is fruitful to the society will be shared with researchers only, without compromising personal data of the participant.