Selective Estrogen Modulation and Melatonin in Early COVID-19

Covid19 Clinical Trial

— SENTINEL  

Official title:

Selective Estrogen Modulation and Melatonin in Early COVID-19

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04531748
• Other study ID #: 20-842
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 2021
• Est. completion date: September 2022

Study information

• Verified date: May 2021
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2022
• Est. primary completion date: September 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Covid19

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Reena Mehra, MD

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak increase in COVID-19 Sign and Symptom score	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.	Screening to 28 days
Secondary	Nadir Oxygen Saturation	Daily mean values	Day 1 through day 14
Secondary	Peak Heart Rate	Daily mean values	Day 1 through day 14
Secondary	Time to COVID-19 Sign and Symptom score resolution	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.	Screening to 28 days
Secondary	Time to WHO 7-point ordinal scale score of 3 or higher	not hospitalized, no limitation of activities (or resumption of normal activity); not hospitalized but limitation on activities; hospitalized, not requiring supplemental oxygen; hospitalized, requiring supplemental oxygen (low-flow, e.g., nasal prong); hospitalized, requiring non-invasive ventilation and/or high-flow oxygen; hospitalized, on invasive ventilation or ECMO; death	Day 1 to Day 30