Treatment of Long CoronaVirus Disease (COVID) (TLC) Feasibility Trial

COVID-19 Clinical 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05946551
• Other study ID #: STUDY00005537
• Status: Recruiting
• Phase: Phase 3
• Start date: March 8, 2024
• Est. completion date: October 2024

Study information

• Verified date: April 2024
• Source: Emory University
• Contact: Tiffany Walker, MD
• Phone: 404-778-1621
• Email: tiffany.austin.walker[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Cetirizine
Cetirizine will be dispensed as a 10mg capsule with instructions for patients to take one capsule daily by mouth, preferably at bedtime.
• Famotidine
Famotidine will be dispensed in 20mg capsules with instructions for patients to take one capsule twice daily, as close to the same times every day as possible.
• Cetirizine Placebo
The cetirizine placebo will be designed as a capsule of an inert substance and will match the morphology of the cetirizine treatment capsule. Administration instructions to match that of cetirizine.
• Famotidine Placebo
The famotidine placebo will be designed as a capsule of an inert substance and will match the morphology of the famotidine treatment capsule. Administration instructions to match that of famotidine.

Locations

Country	Name	City	State
United States	Emory Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Metro-Atlanta	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	CURE Drug Repurposing Collaboratory (CDRC)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The 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 will be recorded as part of the end-of-study survey.	12 weeks post-intervention
Primary	Number of participants that had trouble adhering to the study drug schedule	The number of participants that had trouble adhering to the study drug schedule will be recorded as part of the end-of-study survey.	12 weeks post-intervention
Primary	Number of participants that had any difficulty using the REDCap interface.	The number of participants that had any difficulty using the REDCap interface will be recorded as part of the end-of-study survey.	12 weeks post-intervention
Primary	Number of participants that prefer participating in this virtual study	The number of participants that prefer participating in this virtual study compared to participating in an in-person study hosted at a medical center will be recorded as part of the end-of-study survey.	12 weeks post-intervention
Primary	Number of participants satisfied with their opportunities to interact with study staff	The number of participants satisfied with their opportunities to interact with study staff will be recorded as part of the end-of-study survey.	12 weeks post-intervention
Primary	Number of participants that felt they could reach study staff if needed	The number of participants that felt they could reach study staff if needed will be recorded as part of the end-of-study survey.	12 weeks post-intervention
Primary	Number of participants that felt that study staff was available and easy to contact to report any adverse effects	The number of participants that felt that study staff was available and easy to contact to report any adverse effects that they experienced from the medication will be recorded as part of the end-of-study survey.	12 weeks post-intervention
Primary	Number of participants that felt that the amount of information collected in each series of surveys was acceptable	The number of participants that felt that the amount of information collected in each series of surveys was acceptable will be recorded as part of the end-of-study survey.	12 weeks post-intervention
Primary	Number of participants that felt that the frequency in which the information was collected was acceptable	The number of participants that felt that the frequency in which the information was collected was acceptable will be recorded as part of the end-of-study survey.	12 weeks post-intervention
Primary	Improvement rating	Participants will be asked how much they feel they improved from this treatment over the last 12 week using a scale from 1 to 5, with 5 being complete improvement (better outcome) and 1 being no improvement.	12 weeks post-intervention
Primary	Quality of life (QoL) score rating	Participants will be asked how much their quality of life was impacted by changes to their health during the study. On a scale of 1 to 5 with 5 being the most impacted (better outcome) and 1 being not at all impacted by changes to their health.	12 weeks post-intervention
Primary	Interest score	Participants will be asked how interested they are in continuing treatment with the study medication after the study. On a scale of 1 to 5, with 5 being completely interested (better outcome) and 1 being completely uninterested.	12 weeks post-intervention
Secondary	Proportion of survey completion	Percentage of participants who complete 70% of surveys will be assessed	12 weeks post-intervention
Secondary	Proportion of study drug adherence	Percentage of participants who complete 70% of doses will be assessed	12 weeks post-intervention
Secondary	Proportion of Lost to Follow Up (LFUP)	Percentage of participants Lost to Follow Up (LFUP) will be assessed	12 weeks post-intervention
Secondary	Proportion of voluntary termination	Percentage of participants that voluntarily terminate participation will be assessed	12 weeks post-intervention
Secondary	Adverse events (AEs) incidence	The total number of adverse events in the treatment arms versus the placebo arm will be recorded.	12 weeks post-intervention
Secondary	Serious, unexpected suspected adverse reactions (SUSAR) incidence	The number of SUSARs in the treatment arms versus the placebo arm will be recorded.	12 weeks post-intervention
Secondary	Study-wide serious adverse events (SAEs) incidence	The total number of SAEs in the treatment arms versus the placebo arm will be recorded.	12 weeks post-intervention
Secondary	Number of discontinuations or temporary suspensions of IP	The total number of participants who discontinue any of the treatment arms versus the placebo arm will be recorded.	12 weeks post-intervention