Clinical trial NCT05946551: Treatment of Long CoronaVirus Disease (COVID) (TLC) Feasibility Trial
Official title: Feasibility Assessment of a Decentralized Platform Adaptive Double-Blind, Randomized Controlled Trial Investigating Repurposed Drugs in the Treatment of Post-Acute Sequelae of Coronavirus-19 (PASC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19
Keywords: Long COVID-19
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: CURE Drug Repurposing Collaboratory (CDRC)
First posted: 2023-07-14
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess the feasibility and acceptability of methods and procedures to be employed in a larger scale decentralized platform adaptive randomized clinical trial in patients with a history of a Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Polymerase Chain Reaction (PCR) positive test and/or medical records from a healthcare provider that coincides with the diagnosis of long-COVID.

Detailed description: Fully decentralized single-center, double-blind, randomized, placebo-controlled pilot feasibility trial for patients reporting symptoms consistent with at least one of the following PASC symptoms: Brain fog, Fatigue, Headache, Sleep Disturbance, Post-exertional Malaise (PEM), or Dysautonomia.

Participants' interactions with study staff and the study visits will occur primarily via REDCap and Zoom. Informed consent will be conducted remotely via Zoom and obtained electronically in REDCap. Subjects will complete protocol-required logs, questionnaires, and surveys in REDCap. Dose tolerability assessments will occur via televisit preferably, or phone if necessary.

Following informed consent, subjects will enter a 4-week screening period during which medical records will be obtained and reviewed. At baseline (Day -28) subjects will complete a battery of tests consisting of the World Health Organization Disability Assessment Schedule (WHODAS) 2.0, Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue 7a, Insomnia Severity Scale, PROMIS Cognitive Function 6A, DePaul Symptom Questionnaire - Post-Exertional Malaise (DSQ-PEM) Short Form, Headache Diary, COMPASS 31, and Self-reported persistent symptoms questionnaire. The headache diary requires daily tracking for 7 days (i.e., Day -28- Day -22).

Subjects who complete the screening phase will proceed to randomization where they will be randomized 2:1 to either histamine receptor antagonists (cetirizine and famotidine) or matching placebos. Emory University's Investigational Drug Services (IDS) will conduct the randomization and will overnight via national courier the assigned medication to the study subject. The treatment phase of 12 weeks starts upon ingestion of the first dose.

Cetirizine and famotidine will be supplied as 10mg capsules and 20mg capsules respectively. Dosing for the entire treatment period is one 10mg capsule cetirizine or placebo once daily, preferably at bedtime, and one 20mg capsule famotidine or placebo twice daily, as near as possible to the same time every day. Dose tolerability will be assessed on Day 14 via televisit or phone call. If the dose of either IP is not tolerated, subjects will be removed from the study. If the doses are tolerated, subjects will be resupplied and tolerability assessed per protocol.

Throughout the treatment phase subjects in all arms will complete the symptom questionnaire, adverse event, study drug adherence, and concomitant medication logs weekly. All subjects will complete the full battery of tests on Days 42, 63, and 84 (Weeks 6, 9, and 12). Subjects will have a +/- 3-day window in which to complete the battery. However, the headache diary requires daily tracking for the 7 days preceding Days 43, 63, and 84. On Day 84 all subjects will complete an end-of-study survey assessing their thoughts and feelings about the study methods and procedures.

Eligibility criteria: Inclusion Criteria:

1. Adults ≥18 years of age with a history of a SARS-CoV-2 PCR positive test and/or medical records from a healthcare provider that coincides with the diagnosis of long-COVID
2. New or worsened symptoms since the onset of COVID-19 that are persistent at the time of enrollment and have lasted for ≥ 12 weeks (including at least one of the following: fatigue, post-exertional malaise (PEM), headache, brain fog, sleep disturbance, dysautonomia.
3. Confirmation of negative urine or serum human chorionic gonadotropin (HCG) (pregnancy) test in women of childbearing potential
4. Willing to use appropriate contraceptives for female and male subjects for the duration of the study
5. Has an address (for mailing of study drug) in the state of Georgia
6. Able to swallow capsules
7. Has reliable access to a mobile phone, tablet, laptop, or desktop computer capable of connecting to the internet via Wi-Fi or a data plan
8. Available lab work (CBC and CMP) after the onset of long COVID symptoms
9. Willing and able to comply with scheduled visits, treatment plan, and other study procedures including receiving either intervention or placebo
10. Willing to not take any of the study medications while enrolled in the study except for essential needs as prescribed by a healthcare provider

Exclusion Criteria:

1. No post-acute COVID-19 symptoms (PASC) symptoms at the time of enrollment or PASC symptoms present \<12 weeks at the time of enrollment
2. Inability to provide own informed consent
3. Currently Hospitalized
4. For women of childbearing potential (WOCBP), currently pregnant or plans to become pregnant during the study period; for males with partners of childbearing potential (OCBP), plans to become pregnant during the study period
5. Actively enrolled in another Long COVID/PASC interventional trial or participation in another interventional clinical trial in the last 30 days or planned during the trial period
6. Unstable medical comorbidities (e.g., decompensated cirrhosis, stage III-IV chronic kidney disease, New York Heart Association (NYHA) class III congestive heart failure), per the patient report, telemedicine physical exam, baseline laboratory values (hematology and extended chemistry panels) and/or medical records
7. Other medical conditions occurring after the onset of COVID-19 that can otherwise account for PASC-type symptoms
8. Currently immunocompromised from the following: solid organ transplant, bone marrow transplant (BMT), high dose steroids (\>20mg prednisone per day), immune modulators, or chemotherapy
9. Currently taking opioid analgesics, undergoing treatment for opioid addiction, or taking any other prohibited concomitant medication
10. Opioid dependence or withdrawal syndrome
11. Known sensitivity or adverse reaction to H1 or H2 receptor antagonists, or medication components
12. Suspected or confirmed pregnancy or breastfeeding
13. Participants already on H1 or H2 receptor antagonists within three (3) months of randomization
14. Currently receiving other therapies to treat COVID-19 or Long COVID symptoms, e.g., convalescent plasma, remdesivir, Paxlovid

Primary outcomes:
measure: Number of participants that had any confusion over how to take the study drug, including which pill to take, when to take it, or how many to take
timeFrame: 12 weeks post-intervention
measure: Number of participants that had trouble adhering to the study drug schedule
timeFrame: 12 weeks post-intervention
measure: Number of participants that had any difficulty using the REDCap interface.
timeFrame: 12 weeks post-intervention
measure: Number of participants that prefer participating in this virtual study
timeFrame: 12 weeks post-intervention
measure: Number of participants satisfied with their opportunities to interact with study staff
timeFrame: 12 weeks post-intervention
measure: Number of participants that felt they could reach study staff if needed
timeFrame: 12 weeks post-intervention
measure: Number of participants that felt that study staff was available and easy to contact to report any adverse effects
timeFrame: 12 weeks post-intervention
measure: Number of participants that felt that the amount of information collected in each series of surveys was acceptable
timeFrame: 12 weeks post-intervention
measure: Number of participants that felt that the frequency in which the information was collected was acceptable
timeFrame: 12 weeks post-intervention
measure: Improvement rating
timeFrame: 12 weeks post-intervention
measure: Quality of life (QoL) score rating
timeFrame: 12 weeks post-intervention
measure: Interest score
timeFrame: 12 weeks post-intervention
Secondary outcomes:
measure: Proportion of survey completion
timeFrame: 12 weeks post-intervention
measure: Proportion of study drug adherence
timeFrame: 12 weeks post-intervention
measure: Proportion of Lost to Follow Up (LFUP)
timeFrame: 12 weeks post-intervention
measure: Proportion of voluntary termination
timeFrame: 12 weeks post-intervention
measure: Adverse events (AEs) incidence
timeFrame: 12 weeks post-intervention
measure: Serious, unexpected suspected adverse reactions (SUSAR) incidence
timeFrame: 12 weeks post-intervention
measure: Study-wide serious adverse events (SAEs) incidence
timeFrame: 12 weeks post-intervention
measure: Number of discontinuations or temporary suspensions of IP
timeFrame: 12 weeks post-intervention
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory Hospital
state: Georgia
city: Atlanta
country: United States
facility: Metro-Atlanta
state: Georgia
Study officials:
affiliation: Emory University
name: Tiffany Walker, MD
role: PRINCIPAL_INVESTIGATOR
References: