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

Primary Purpose

Covid19

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Toremifene

Melatonin

Placebo

About this trial

This is an interventional treatment trial for Covid19 focused on measuring covid19, coronavirus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Toremifene + Melatonin

Melatonin + Placebo

Placebo

Arm Description

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.

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).

Oral placebo will be used with the same number and appearance to the pills as the interventions

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Nadir Oxygen Saturation

Daily mean values

Peak Heart Rate

Daily mean values

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.

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

Full Information

NCT ID

NCT04531748

First Posted

August 27, 2020

Last Updated

May 5, 2021

Sponsor

Reena Mehra, MD

1. Study Identification

Unique Protocol Identification Number

NCT04531748

Brief Title

Selective Estrogen Modulation and Melatonin in Early COVID-19

Acronym

SENTINEL

Official Title

Selective Estrogen Modulation and Melatonin in Early COVID-19

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Withdrawn

Why Stopped

Funding

Study Start Date

December 2021 (Anticipated)

Primary Completion Date

September 2022 (Anticipated)

Study Completion Date

September 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Reena Mehra, MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Covid19

Keywords

covid19, coronavirus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

The Medical Safety Officer will not be blinded.

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Toremifene + Melatonin

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Melatonin + Placebo

Arm Type

Active Comparator

Arm Description

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).

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Oral placebo will be used with the same number and appearance to the pills as the interventions

Intervention Type

Drug

Intervention Name(s)

Toremifene

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Melatonin

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Peak increase in COVID-19 Sign and Symptom score

Description

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 Frame

Screening to 28 days

Secondary Outcome Measure Information:

Title

Nadir Oxygen Saturation

Description

Daily mean values

Time Frame

Day 1 through day 14

Title

Peak Heart Rate

Description

Daily mean values

Time Frame

Day 1 through day 14

Title

Time to COVID-19 Sign and Symptom score resolution

Description

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 Frame

Screening to 28 days

Title

Time to WHO 7-point ordinal scale score of 3 or higher

Description

Time Frame

Day 1 to Day 30

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Reena Mehra, MD

Organizational Affiliation

The Cleveland Clinic

Official's Role

Principal Investigator

12. IPD Sharing Statement

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Selective Estrogen Modulation and Melatonin in Early COVID-19

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