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Selective Estrogen Modulation and Melatonin in Early COVID-19 (SENTINEL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04531748
Recruitment Status : Not yet recruiting
First Posted : August 28, 2020
Last Update Posted : October 29, 2020
Sponsor:
Information provided by (Responsible Party):
Reena Mehra, MD, The Cleveland Clinic

Brief Summary:
This study is a randomized, double-blind, controlled clinical trial to evaluate the effects of toremifene and/or melatonin in adults with mild COVID-19.

Condition or disease Intervention/treatment Phase
Covid19 Drug: Toremifene Drug: Melatonin Other: Placebo Phase 2

Detailed Description:

This study is a randomized, double-blind, controlled clinical trial to evaluate the effects of a 14 day intervention of toremifene plus melatonin or melatonin in adults with mild COVID-19.

The study will evaluate the progression of clinical signs and symptoms (fever, dyspnea, cough, fatigue daily score) and any adverse outcomes in comparison to placebo for 30 days.

The successful completion of this project offers high potential to identify effective treatment (e.g., toremifene plus melatonin and/or melatonin) rapidly for patients with early COVID-19 and to provide, important, fundamental mechanistic insights.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 390 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The Medical Safety Officer will not be blinded.
Primary Purpose: Treatment
Official Title: Selective Estrogen Modulation and Melatonin in Early COVID-19
Estimated Study Start Date : December 2020
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Toremifene + Melatonin

100mg oral Melatonin on Days 1 & 2 (40mg in the morning and 60mg in the evening), 60 mg on Days 3-14, (20mg in the morning and 40mg in the evening).

60mg oral toremifene daily days 1-14.

Drug: Toremifene
Participants will be instructed to take 60mg of oral toremifene capsule daily, 30 minutes before bedtime.

Drug: Melatonin
Participants will be instructed to take the pills orally around the same time in the morning and 30 minutes prior to bedtime in the evening.

Active Comparator: Melatonin + Placebo
100mg oral Melatonin on Days 1 & 2 (40mg in the morning and 60mg in the evening) and 60 mg on Days 3-14, (20mg in the morning and 40mg in the evening).
Drug: Melatonin
Participants will be instructed to take the pills orally around the same time in the morning and 30 minutes prior to bedtime in the evening.

Other: Placebo
Oral placebo will be used with the same number and appearance to the pills as the interventions.

Placebo Comparator: Placebo
Oral placebo will be used with the same number and appearance to the pills as the interventions
Other: Placebo
Oral placebo will be used with the same number and appearance to the pills as the interventions.




Primary Outcome Measures :
  1. Peak increase in COVID-19 Sign and Symptom score [ Time Frame: Screening to 28 days ]
    Score total of 0-12 assessed daily. Each category based on severity of symptoms of Cough, Shortness of breath, Fatigue/tiredness and daily temperature on a rating scale of 0-3.


Secondary Outcome Measures :
  1. Nadir Oxygen Saturation [ Time Frame: Day 1 through day 14 ]
    Daily mean values

  2. Peak Heart Rate [ Time Frame: Day 1 through day 14 ]
    Daily mean values

  3. Time to COVID-19 Sign and Symptom score resolution [ Time Frame: Screening to 28 days ]
    Score total of 0-12 assessed daily. Each category based on severity of symptoms of Cough, Shortness of breath, Fatigue/tiredness and daily temperature on a rating scale of 0-3.

  4. Time to WHO 7-point ordinal scale score of 3 or higher [ Time Frame: Day 1 to Day 30 ]
    1. not hospitalized, no limitation of activities (or resumption of normal activity)
    2. not hospitalized but limitation on activities
    3. hospitalized, not requiring supplemental oxygen
    4. hospitalized, requiring supplemental oxygen (low-flow, e.g., nasal prong)
    5. hospitalized, requiring non-invasive ventilation and/or high-flow oxygen
    6. hospitalized, on invasive ventilation or ECMO
    7. death



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical testing positive for SARS-Cov-2 by standard RT-PCR or equivalent test
  • Willing and able to give informed consent for participation in the study and agrees with the study and its conduct
  • Age>18 years
  • Fluency in English or Spanish language, functional literacy
  • Able to swallow pills
  • COVID-19 Daily Sign and Symptom score of 2-8

Exclusion Criteria:

  • History of deep venous thrombosis or pulmonary embolism
  • Hypercoagulable disorders (e.g. lupus anticoagulant, deficiency of protein C or S)
  • Embolic stroke
  • Liver disease
  • History of endometrial cancer
  • Menopausal hormone therapy or oral, injectable or transdermal contraceptives
  • Depression which is not optimally treated (assessed via medical record and patient will be asked if she/he feels that depression is optimally treated)
  • Medications which prolong the QT interval (e.g. hydroxychloroquine or azithromycin) or those with long QT syndrome (heritable or acquired). Examples of other medications which prolong the QT interval include: Agents generally accepted to prolong QT interval include Class 1A (e.g., quinidine, procainamide, disopyramide) and Class III (e.g., amiodarone, sotalol, ibutilide, dofetilide) antiarrhythmics; certain antipsychotics (e.g., thioridazine, haloperidol); certain antidepressants (e.g., venlafaxine, amitriptyline); certain antibiotics (e.g., erythromycin, clarithromycin, levofloxacin, ofloxacin); and certain anti-emetics (e.g., ondansetron, granisetron) (Please refer to Appendix for detailed list of medications)
  • Inability to participate in follow up assessment
  • Dementia/cognitive dysfunction
  • Pregnancy (pregnancy testing will be performed to determine eligibility)
  • Breastfeeding
  • Participating in other COVID-19 trials
  • Immunodeficiency (including HIV, Hepatitis C, bone marrow transplant history, on immunosuppressant medications)
  • Current hospitalization
  • Seizure disorder
  • History of rheumatoid arthritis
  • Heart failure (NYHA Class III or IV)
  • Current diagnosis of renal insufficiency/failure
  • QTc >470ms per 12-lead ECG
  • Calcium >10.2mg/dL
  • AST or ALT > 2x upper limit of normal (ULN)
  • D-dimer >= 1000 u/L
  • Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2
  • On other treatment(s) for COVID-19 (e.g. hydroxychloroquine, remdesivir)
  • Anticoagulant medications (e.g. coumadin, glycoprotein IIa/IIIb inhibitors)
  • Clinical signs of severe or critical severity of COVID-19 (e.g. shortness of breath at rest, Respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air)
  • Use of supplemental oxygen
  • Moderate to severe pulmonary disease up to PI discretion

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04531748


Contacts
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Contact: Samantha Wells 3162152759 wellss@ccf.org
Contact: Kylie Phillips 2164451593 philik3@ccf.org

Sponsors and Collaborators
Reena Mehra, MD
Investigators
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Principal Investigator: Reena Mehra, MD The Cleveland Clinic
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Responsible Party: Reena Mehra, MD, Director, Sleep Disorders Research, Neurological Institute, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT04531748    
Other Study ID Numbers: 20-842
First Posted: August 28, 2020    Key Record Dates
Last Update Posted: October 29, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Reena Mehra, MD, The Cleveland Clinic:
covid19
coronavirus
Additional relevant MeSH terms:
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Toremifene
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents