Selective Estrogen Modulation and Melatonin in Early COVID-19

NCT ID: NCT04531748

Last Updated: 2021-05-10

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-31
• Study Completion Date: 2022-09-30

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Toremifene

Intervention Type: DRUG

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

Melatonin

Intervention Type: DRUG

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.

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).

Group Type: ACTIVE_COMPARATOR

Melatonin

Intervention Type: DRUG

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.

Placebo

Intervention Type: OTHER

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

Toremifene

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

Intervention Type: 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.

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Reena Mehra, MD

OTHER

Sponsor Role: lead

Responsible Party

Reena Mehra, MD

Director, Sleep Disorders Research, Neurological Institute

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Reena Mehra, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Other Identifiers

20-842

Identifier Type: -

Identifier Source: org_study_id