Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia

NCT05542095 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: SimCA Trial
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Olfactory dysfunction (OD) or changes in smell and/or taste is one of the cardinal presenting symptoms of COVID-19. Despite the prevalence of COVID and resultant OD, the pathophysiology of COVID-mediated OD is not fully understood, but recent evidence indicates that local inflammatory and oxidative injury play a major role. This phase 1 safety trial evaluates the use of simvastatin nasal irrigations for the management of COVID-mediated OD. We will determine the maximum tolerable dose and evaluate the safety and tolerability of high-volume simvastatin nasal irrigations in subjects with persistent COVID-mediated OD. Each subject will complete bloodwork at baseline and then at the completion of their participation in the study. During this trial, we will observe olfactory function for each participant at baseline and completion of this study via the University of Pennsylvania Smell Identification Test (UPSIT). Investigational product will be shipped directly to the subject for daily irrigation each day for 4 weeks. Weekly throughout the study for a total of 4 weeks, subjects will complete the Sino-Nasal Outcome Test-22. The current study would provide the support for Phase II and III clinical trials. Additionally, the study has applications for other disease processes affecting the sinonasal cavities.

Conditions

Olfactory Disorder; COVID-19

Keywords

Olfactory Disorder; COVID-19

Outcome Measures

Primary Outcomes (1)

• Safety and feasibility of simvastatin nasal wash

  Primary objective is to evaluate safety and feasibility of simvastatin nasal wash. * Successive cohorts of 3 subjects will be enrolled until dose-limiting toxicities (DLT; defined as the development of statin intolerance with liver toxivity or muscle toxicity as determined by elevated AST, ALT, or CK or the development of significant systemic or sinonasal symptoms requiring drug discontinuation) are observed in greater than 33% of the enrolled subjects. We will monitor for signs or symptoms of toxicity. * Weekly throughout the study, subjects will complete the SNOT-22. The absolute change in SNOT-22 scores from baseline will be utilized to describe any adverse effects of simvastatin rinses on sinonasal function and quality of life. * Nasal endoscopy will be performed at the time of enrollment and at study completion to ensure no local tissue effects of topical simvastatin rinses. A Lund-Kennedy score reflecting sinonasal disease severity will be noted at the time of nasal endoscopy.

  4 weeks

Secondary Outcomes (1)

• Maximum tolerable dose of simvastatin nasal rinses via a dose escalation trial.

  4 weeks

Study Arms (4)

topical nasal simvastatin - 0.1 mg dose

EXPERIMENTAL

topical nasal simvastatin - 0.1 mg dose Subjects are entered into the study in groups of 3. This first cohort will receive the lowest dose of simvastatin (0.1mg) via nasal irrigation for 4 weeks. If none of the 3 subjects report toxicity, the next group of 3 subjects enrolled will receive the consecutive higher dose of simvastatin for 1 month. If \>2 of the 3 subjects enrolled in the first group report toxicity then the dose is considered toxic or "MTD is exceeded." If 1 of the first 3 reports toxicity, then the next group of 3 enrolled subjects will receive the same dose as group 1. When 6 subjects receive the same dose, and \<1 of them report toxicity, the consecutive group of 3 subjects will receive the successive higher dose. If \>2 of the 6 subjects on the same dose report toxicities, then MTD is exceeded. Intra-patient dose escalation will not be performed.

Drug: Simvastatin

topical nasal simvastatin - 0.25 mg dose

EXPERIMENTAL

topical nasal simvastatin - 0.25 mg dose Subjects are entered into the study in groups of 3. This 2nd cohort will receive the 0.25mg simvastatin via nasal irrigation for 4 weeks. If none of the 3 subjects report toxicity, the next group of 3 subjects enrolled will receive the consecutive higher dose of simvastatin for 1 month. If \>2 of the 3 subjects enrolled in the first group report toxicity then the dose is considered toxic or "MTD is exceeded." If 1 of the first 3 reports toxicity, then the next group of 3 enrolled subjects will receive the same dose as group 1. When 6 subjects receive the same dose, and \<1 of them report toxicity, the consecutive group of 3 subjects will receive the successive higher dose. If \>2 of the 6 subjects on the same dose report toxicities, then MTD is exceeded. Intra-patient dose escalation will not be performed.

Drug: Simvastatin

topical nasal simvastatin - 0.5 mg dose

EXPERIMENTAL

topical nasal simvastatin - 0.5 mg dose Subjects are entered into the study in groups of 3. This 3rd cohort will receive the 0.5mg simvastatin via nasal irrigation for 4 weeks. If none of the 3 subjects report toxicity, the next group of 3 subjects enrolled will receive the consecutive higher dose of simvastatin for 1 month. If \>2 of the 3 subjects enrolled in the first group report toxicity then the dose is considered toxic or "MTD is exceeded." If 1 of the first 3 reports toxicity, then the next group of 3 enrolled subjects will receive the same dose as group 1. When 6 subjects receive the same dose, and \<1 of them report toxicity, the consecutive group of 3 subjects will receive the successive higher dose. If \>2 of the 6 subjects on the same dose report toxicities, then MTD is exceeded. Intra-patient dose escalation will not be performed.

Drug: Simvastatin

topical nasal simvastatin - 1 mg dose

EXPERIMENTAL

topical nasal simvastatin - 1 mg dose Subjects are entered into the study in groups of 3. This 4th cohort will receive the 1mg simvastatin via nasal irrigation for 4 weeks. If none of the 3 subjects report toxicity, then the drug will be considered tolerated at the maximum tested dose. If \>2 of the 3 subjects enrolled in the first group report toxicity then the dose is considered toxic or "MTD is exceeded." If 1 of the first 3 reports toxicity, then the next group of 3 enrolled subjects will receive the same dose as group 1. When 6 subjects receive the same dose, and \<1 of them report toxicity, then this maximum dose is considered tolerable. If \>2 of the 6 subjects on the same dose report toxicities, then MTD is exceeded. Intra-patient dose escalation will not be performed.

Drug: Simvastatin

Interventions

Simvastatin DRUG

Compounded simvastatin that is suspended within a nasal saline irrigation will be utilized throughout this study. Participants will suspend the contents of the simvastatin capsules (0.1mg, 0.25 mg, 0.5 mg, and 1 mg) into the sinus rinse bottle containing nasal saline. All participants will receive an 8-ounce sinus rinse bottle and a 4-week supply of USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture (pH balanced, Isotonic \& Preservative \& Iodine Free) commercially prepared packets. Participants will either need to purchase distilled water or boil tap water for five minutes for use with the saline irrigation.

Also known as: ZOCOR

topical nasal simvastatin - 0.1 mg dose; topical nasal simvastatin - 0.25 mg dose; topical nasal simvastatin - 0.5 mg dose; topical nasal simvastatin - 1 mg dose

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females age 18-70 years old
• Diagnosis of COVID-19 at least 3 months prior to study enrollment, but no greater than 12 months prior to study.
• Objective olfactory dysfunction, believed to be due to COVID-19, that has persisted despite viral recovery otherwise (initial score on the UPSIT consistent with decreased olfactory function (\<= 34 in women, \<=33 in men)
• Not currently using concomitant therapies specifically for the treamtment of OD, or willing to discontinue other therapies for the treatment of OD for the duration of the trial
• Ability to read, write, and understand English

You may not qualify if:

• Olfactory loss prior to COVID-19 infection
• History of conditions that impact olfactory function
• Chronic rhinosinusitis
• History of prior sinonasal or skullbase surgery
• Neurodegenerative disorders (Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, Lewy body dementia, frontotemporal dementia)
• Current or recent (within 8 weeks of study enrollment) oral statin use
• History of conditions that increase risks of statin intolerance
• Untreated hypothyroidism
• History of chronic kidney disease or abnormal renal function at the time of enrollment
• Personal or family history of myositis or elevated creatine kinase at the time of enrollment
• Alcohol consumption greater than 7 drinks per week (female) or 14 drinks per week (male)
• History of liver disease or elevated liver enzymes at the time of enrollment
• History of statin intolerance
• Human immunodeficiency virus
• Viral hepatitis

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Duke University: collaborator

MeSH Terms

Conditions

COVID-19

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Nyssa F Farrell, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Otolaryngology

Model Details: This is an open-label phase 1 trial of topical simvastatin delivered via nasal irrigation using a standard three plus three (3+3) dose-escalation design. Subjects are entered into the study in groups of 3. The study will continue with successive cohorts of 3 subjects until dose-limiting toxicities (DLT) are observed in greater than 33% of the enrolled subjects. DLT is defined as the development of statin intolerance with liver toxicity or muscle toxicity or the development of significant systemic or sinonasal symptoms requiring drug discontinuation. The first cohort will receive the lowest dose of simvastatin (0.1mg) via nasal irrigation for 4 weeks. The next group of 3 subjects will receive the consecutive higher dose of simvastatin. We anticipate that 4 doses will be trialed (0.1 mg, 0.25 mg, 0.5 mg, 1 mg) within the predetermined safety range.

Study Record Dates

• First Submitted: September 13, 2022
• First Posted: September 15, 2022
• Study Start: May 1, 2023
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: June 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share