Covid19Phase 2SENTINELNCT04531748
Selective Estrogen Modulation and Melatonin in Early COVID-19
A Phase 2 study testing Toremifene and Melatonin in people with Covid19, run by Reena Mehra, MD.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Toremifene and Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2021to Sep 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 29Show fewer
- 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
About this study
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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToremifeneDrug
Participants will be instructed to take 60mg of oral toremifene capsule daily, 30 minutes before bedtime.
MelatoninDrug
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.
PlaceboOther
Oral placebo will be used with the same number and appearance to the pills as the interventions.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Drug: Melatonin; Other: Placebo |
| Placebo | Placebo comparator | Oral placebo will be used with the same number and appearance to the pills as the interventions Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Screening to 28 days
Secondary outcomes (4)
Nadir Oxygen Saturation
Daily mean values
Measured: Day 1 through day 14
Peak Heart Rate
Daily mean values
Measured: Day 1 through day 14
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.
Measured: Screening to 28 days
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
Measured: Day 1 to Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2020
- Study startDec 2021 (estimated)
- Primary completionSep 2022 (estimated)
- Study completionSep 2022 (estimated)
Why it stopped: Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Reena Mehra, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Reena Mehra, MD, The Cleveland Clinic
- Investigators
- Reena Mehra, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04531748
- Sponsor's protocol ID
- 20-842
- Acronym
- SENTINEL
- Status last verified
- May 2021
- First submitted
- 27 Aug 2020
- Last updated
- 10 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selective Estrogen Modulation and Melatonin in Early COVID-19
- ClinicalTrials.gov ID
- NCT04531748
- Acronym / sponsor ID
- SENTINEL / 20-842
- Conditions
- Covid19
- Keywords
- covid19, coronavirus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Reena Mehra, MDUniversity, hospital or other
- Study start
- Dec 2021 (estimated)
- Primary completion
- Sep 2022 (estimated)
- Study completion
- Sep 2022 (estimated)
- First posted
- 28 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Toremifene + Melatonin | Active comparator | Drug: Toremifene, Drug: Melatonin100mg 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. |
| Melatonin + Placebo | Active comparator | Drug: Melatonin, Other: Placebo100mg 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). |
| Placebo | Placebo comparator | Other: PlaceboOral placebo will be used with the same number and appearance to the pills as the interventions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ToremifeneParticipants will be instructed to take 60mg of oral toremifene capsule daily, 30 minutes before bedtime. | Drug | Toremifene + Melatonin |
| MelatoninParticipants will be instructed to take the pills orally around the same time in the morning and 30 minutes prior to bedtime in the evening. | Drug | Melatonin + Placebo, Toremifene + Melatonin |
| PlaceboOral placebo will be used with the same number and appearance to the pills as the interventions. | Other | Melatonin + Placebo, Placebo |
Primary outcome
Peak increase in COVID-19 Sign and Symptom score
Time frame: 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.
4 secondary outcomes
Nadir Oxygen Saturation
Time frame: Day 1 through day 14
Peak Heart Rate
Time frame: Day 1 through day 14
Time to COVID-19 Sign and Symptom score resolution
Time frame: Screening to 28 days
Time to WHO 7-point ordinal scale score of 3 or higher
Time frame: Day 1 to Day 30
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2021.
Related trials for Covid19
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Not yet recruitingPhase 3
Dapagliflozin for Long COVID Syndrome
COVID - 19, Long COVID Syndrome
RecruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruitingObservational study
Analysis of Coronavirus Disease 19 (COVID-19) Convalescent Plasma
Asymptomatic COVID-19 Infection Laboratory-Confirmed, Symptomatic COVID-19 Infection Laboratory-Confirmed
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reena Mehra, MD principal investigator
The Cleveland Clinic
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toremifene and Melatonin in people with Covid19, run by Reena Mehra, MD.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 May 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak increase in COVID-19 Sign and Symptom score (time frame: Screening to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2021.