SENTINEL: Selective Estrogen Modulation and Melatonin in Early COVID-19

Sponsor

Reena Mehra, MD (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04531748

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 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

Anticipated Study Start Date :

Dec 1, 2021

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Peak increase in COVID-19 Sign and Symptom score [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

Nadir Oxygen Saturation [Day 1 through day 14]
Daily mean values
Peak Heart Rate [Day 1 through day 14]
Daily mean values
Time to COVID-19 Sign and Symptom score resolution [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.
Time to WHO 7-point ordinal scale score of 3 or higher [Day 1 to Day 30]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Reena Mehra, MD

Investigators

Principal Investigator: Reena Mehra, MD, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

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:

Aug 28, 2020

Last Update Posted:

May 10, 2021

Last Verified:

May 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Reena Mehra, MD, Director, Sleep Disorders Research, Neurological Institute, The Cleveland Clinic

covid19

coronavirus

Additional relevant MeSH terms:

COVID-19

Toremifene

Melatonin

Study Results

No Results Posted as of May 10, 2021