Selective Estrogen Modulation and Melatonin in Early COVID-19

NCT04531748 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 20-842
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Covid19

Keywords

covid19; coronavirus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Nadir Oxygen Saturation

  Day 1 through day 14

• Peak Heart Rate

  Day 1 through day 14

• Time to COVID-19 Sign and Symptom score resolution

  Screening to 28 days

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

  Day 1 to Day 30

Study Arms (3)

Toremifene + Melatonin

ACTIVE COMPARATOR

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; Drug: Melatonin

Melatonin + Placebo

ACTIVE COMPARATOR

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; Other: Placebo

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Toremifene DRUG

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

Toremifene + Melatonin

Melatonin 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; Toremifene + Melatonin

Placebo OTHER

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

Melatonin + Placebo; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Reena Mehra, MD: lead

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

Toremifene; Melatonin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Tamoxifen; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Reena Mehra, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Medical Safety Officer will not be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Sleep Disorders Research, Neurological Institute

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: August 28, 2020
• Study Start: December 1, 2021
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: May 10, 2021

Record last verified: 2021-05