Ibudilast + Pentoxifylline for Long COVID

(RECLAIM Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by George Tomlinson, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Waitlist Available

Sponsor: University Health Network, Toronto

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial will test two treatments to find the best way to help people with long-term COVID-19 symptoms. It will adapt based on early results, stopping ineffective treatments and adding new ones as needed.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be on standard of care therapies for at least 4 weeks before joining the trial.

What data supports the idea that Ibudilast + Pentoxifylline for Long COVID is an effective drug?

The available research does not provide direct evidence supporting the effectiveness of Ibudilast + Pentoxifylline for Long COVID. The studies focus on Pentoxifylline's effects in other conditions, such as cancer-related muscle wasting and multiple sclerosis. For example, Pentoxifylline has been shown to prevent muscle loss in cancer patients and improve treatment outcomes in multiple sclerosis when combined with another drug. However, these findings do not directly relate to Long COVID. ^{1 2 3 4 5}

What safety data is available for the treatment of Ibudilast + Pentoxifylline for Long COVID?

The provided research does not contain specific safety data for the combination of Ibudilast (also known as MN-166, AV-411, Ketas) and Pentoxifylline (also known as Trental) for Long COVID. The studies focus on whey protein and its effects, which are unrelated to the safety of Ibudilast and Pentoxifylline. Therefore, no relevant safety data for this treatment combination is available in the provided research. ^{6 7 8 9 10}

Is the drug Ibudilast, Pentoxifylline, Placebo, Whey Protein Isolate promising for Long COVID?

The information provided does not include any relevant research articles or data about the effectiveness of Ibudilast, Pentoxifylline, Placebo, or Whey Protein Isolate for Long COVID. Therefore, we cannot determine if it is a promising treatment based on the given information. ^{11 12 13 14 15}

Research Team

Peter Juni, MD, PhD

Principal Investigator

Oxford University, UK

Angela M Cheung, MD,PhD

Principal Investigator

University Health Network, Toronto

George Tomlinson, PhD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

Adults over 18 with Long COVID symptoms persisting for more than 3 months since the earliest of a positive test or symptom onset, and who have been symptomatic for at least 2 months. Participants must have tried standard care therapies for 4 weeks, be able to consent, follow study rules, and if capable of childbearing, agree to use approved contraception methods. Excludes those who had severe COVID requiring mechanical ventilation or ECMO, current severe organ failure or transplant patients.

Inclusion Criteria

I am 18 years old or older.

I have had COVID-19 symptoms for more than 3 months since I first got sick.

I have been on standard cancer treatment for at least 4 weeks.

Exclusion Criteria

I cannot undergo any of the treatments offered in this study due to health reasons.

I was on a ventilator or ECMO for COVID-19 treatment.

I do not have organ failure, haven't had an organ transplant, and am not in the hospital.

Treatment Details

Interventions

• Ibudilast (Other)
• Pentoxifylline (Other)
• Placebo (Other)
• Whey Protein Isolate (Dietary Supplement)

Trial Overview The RECLAIM trial is testing Ibudilast and Pentoxifylline against a placebo in Canadian patients with Long COVID. It's an adaptive trial that can modify its arms based on effectiveness results during the process. Treatment lasts two months with four additional months of follow-up to evaluate recovery from lingering symptoms.

Participant Groups

Group I: PENTOXIFYLLINE Experimental Treatment 1 Intervention

Participants will receive a 400mg dose (1 pill) 3 times per day taken by mouth.

Group II: IBUDILAST Experimental Treatment 1 Intervention

Participants will receive 20 mg dose (2 pills) twice per day taken by mouth.

Group III: PLACEBO Placebo Group 1 Intervention

Participants will receive 2 placebo pills twice per day taken by mouth OR 1 placebo pill 3 times a day taken by mouth.

Ibudilast is already approved in Japan for the following indications:

Approved in Japan as Ibudilast for:

• Bronchial asthma
• Cerebral vasospasm following subarachnoid hemorrhage

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Dr. Brad Wouters

University Health Network, Toronto

Chief Medical Officer since 2020

MD from University of Toronto

Dr. Kevin Smith

University Health Network, Toronto

Chief Executive Officer since 2018

Professor at McMaster University and University of Toronto

Findings from Research

Sarcopenia and muscle wasting are expected to increase in older adults due to COVID-19 hospitalizations and lockdowns, driven by factors like physical inactivity and poor diet.

Supplementing meals with whey protein-enriched enteral products, which provide 3-5 g of leucine, can effectively stimulate muscle protein synthesis in older adults, potentially helping to mitigate the risk of sarcopenia during prolonged periods of inactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mTOR1c Activation with the Leucine "Trigger" for Prevention of Sarcopenia in Older Adults During Lockdown. Mai, K., Cando, P., Trasino, SE.[2022]

The EFSA Panel concluded that whey basic protein isolate from skimmed cow's milk is safe for human consumption, including its use in infant formulas and food supplements, based on a review of its safety in 2018.

The Panel determined that extending the use of whey basic protein isolate in infant formulas and food supplements would not increase the potential intake beyond previously assessed levels, confirming its safety at these new proposed uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of whey basic protein isolate for extended uses in foods for special medical purposes and food supplements for infants pursuant to Regulation (EU) 2015/2283. Turck, D., Castenmiller, J., de Henauw, S., et al.[2020]

The combination of fluticasone furoate (FF) and vilanterol trifenatate (VI) offers a once-daily dosing option for asthma management, which may improve patient adherence compared to traditional twice-daily inhalers.

Clinical studies show that FF/VI at doses of 100/25µg and 200/25µg provide similar improvements in lung function and asthma control as the twice-daily combination of fluticasone propionate and salmeterol, with comparable side effect rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluticasone furoate and vilanterol trifenatate combination therapy for the treatment of asthma. Gray, EL., Chang, V., Thomas, PS.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Manipulation of the ubiquitin-proteasome pathway in cachexia: pentoxifylline suppresses the activation of 20S and 26S proteasomes in muscles from tumor-bearing rats. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Pentoxifylline therapy for chronic claudication: are patients dependent on therapy? [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

PTX Treatment of Colon Cancer: Mode of Action Based on Tumor Marker and Cytokine Kinetics. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Synergistic immunomodulatory effects of interferon-beta1b and the phosphodiesterase inhibitor pentoxifylline in patients with relapsing-remitting multiple sclerosis. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of Beta-lactoglobulin as a Novel food pursuant to Regulation (EU) 2015/2283. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

mTOR1c Activation with the Leucine "Trigger" for Prevention of Sarcopenia in Older Adults During Lockdown. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Inhibitory effect of whey protein concentrate on SARS-CoV-2-targeted furin activity and spike protein-ACE2 binding in methotrexate-induced lung damage. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Safety of whey basic protein isolate for extended uses in foods for special medical purposes and food supplements for infants pursuant to Regulation (EU) 2015/2283. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Combined effect of dietary supplementation with pressurized whey and exercise training in chronic obstructive pulmonary disease: a randomized, controlled, double-blind pilot study. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Fluticasone furoate and vilanterol trifenatate combination therapy for the treatment of asthma. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Next generation beta adrenoreceptor agonists for the treatment of asthma. [2018]

13. England pubmed.ncbi.nlm.nih.gov

▼Olodaterol--another LABA for COPD. [2016]

14. England pubmed.ncbi.nlm.nih.gov

Double-blind trial of a long-acting bronchodilator preparation ("Nethaprin Dospan") in bronchospastic disease. [2019]

15. United States pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacodynamics and pharmacokinetics of umeclidinium and vilanterol alone and in combination: a randomized crossover trial. [2021]