Lumbrokinase for Long COVID

Overseen By Mackenzie Doerstling, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Autoimmune conditions, Pregnancy, Bleeding disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how Lumbrokinase, a supplement derived from earthworms, might aid individuals with Long COVID, Post-treatment Lyme disease syndrome (PTLDS), or Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Researchers aim to determine if taking Lumbrokinase twice daily for six weeks can alleviate symptoms associated with these conditions. The trial suits those diagnosed by a doctor with one of these conditions and currently experiencing symptoms. As a Phase 1 and Phase 2 trial, the research focuses on understanding the treatment's effects in people and assessing its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking any antiplatelet or anticoagulation medications before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Lumbrokinase, a natural enzyme from earthworms, affects blood clotting and inflammation. It can help break down fibrin, a protein involved in clot formation, potentially reducing blood clots.

Lumbrokinase is generally well-tolerated. Some studies have reported mild side effects like nausea or dizziness, but these are uncommon. Its safe use for other health issues suggests it could be safe for new applications such as Long COVID, Post-treatment Lyme disease syndrome, and Myalgic encephalomyelitis/chronic fatigue syndrome.

This trial is in its early stages, focusing on collecting more safety data. Early-phase trials typically test new treatments on a small group to ensure safety before progressing to larger studies. Safety is closely monitored, and any side effects will be reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Lumbrokinase is unique because it is derived from earthworms and has a different mechanism of action compared to most treatments for Long COVID, which often include antivirals or anti-inflammatory drugs. Unlike these standard options, lumbrokinase works by breaking down fibrin, a protein involved in blood clotting, potentially improving blood flow and reducing symptoms related to fatigue and malaise. Researchers are excited about this treatment because it offers a novel approach that targets the possible underlying vascular issues in Long COVID, which could lead to more effective symptom relief.

What evidence suggests that this trial's treatments could be effective for Long Covid, Post-treatment Lyme disease syndrome, and Myalgic encephalomyelitis/chronic fatigue syndrome?

This trial will evaluate lumbrokinase's effectiveness for various conditions, including Long COVID, Post-treatment Lyme Disease Syndrome (PTLDS), and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Research has shown that lumbrokinase, an enzyme that breaks down blood clots, might benefit these conditions. Studies suggest it can help with blood clotting and overactive platelets, common in these conditions. Early findings indicate that lumbrokinase might improve symptoms by addressing these issues. Although more research is needed, these initial results are promising for its effectiveness. ^{1 3 4 5 6}

Who Is on the Research Team?

David Putrino, PhD, PT

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for individuals with Long Covid, Post-treatment Lyme disease syndrome (PTLDS), or Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specific eligibility criteria are not provided.

Inclusion Criteria

I had or was suspected to have COVID-19 at least 3 months ago.

Baseline EQ-VAS ≤70; EQ-VAS before the index infection ≥80

I meet the criteria for ME/CFS with active symptoms.

Exclusion Criteria

Known allergy to earthworms

I have been diagnosed with an autoimmune condition.

Pregnancy or lactation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Boluoke® brand lumbrokinase capsules, 300,000 functional units (FUs) twice per day, daily for 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lumbrokinase

Trial Overview The trial is testing Lumbrokinase (LK) as a potential treatment in three separate groups: those with Long Covid, PTLDS, and ME/CFS. It's a pilot study to see if the treatment is feasible.

How Is the Trial Designed?

Group I: Post-treatment Lyme Disease Syndrome Experimental Treatment 1 Intervention

Boluoke® brand lumbrokinase capsules, 300,000 functional units (FUs) twice per day, daily for 6 weeks.

Group II: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Experimental Treatment 1 Intervention

Boluoke® brand lumbrokinase capsules, 300,000 functional units (FUs) twice per day, daily for 6 weeks.

Group III: Long Covid Experimental Treatment 1 Intervention

Boluoke® brand lumbrokinase capsules, 300,000 functional units (FUs) twice per day, daily for 6 weeks.

Lumbrokinase is already approved in China, United States, Japan for the following indications:

Approved in China as Lumbrokinase for:

• Cardiovascular diseases
• Stroke prevention
• Myocardial infarction prevention

Approved in United States as Boluoke for:

• Supplement for cardiovascular health
• Blood clot prevention

Approved in Japan as Lumbrokinase for:

• Cardiovascular diseases
• Stroke prevention

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

PolyBio Research Foundation

Collaborator

Trials

3

Recruited

250+

PolyBio Research Foundation

Collaborator

Published Research Related to This Trial

Lumbrokinase (LK), an enzyme from earthworms, shows promising antithrombotic effects, as grafts treated with LK remained patent (open) for longer periods compared to untreated grafts in a rabbit model.

The study found that grafts treated with LK using a covalent bonding method were effective for up to 4 weeks, while those treated by simple dipping were occluded by thrombus after 2 weeks, indicating that the method of application significantly impacts efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo evaluation of lumbrokinase, a fibrinolytic enzyme extracted from Lumbricus rubellus, in a prosthetic vascular graft. Hwang, CM., Kim, DI., Huh, SH., et al.[2016]

Lumbrokinase, a fibrinolytic enzyme from earthworms, was successfully expressed in the milk of lactating goats using a mammary-gland-specific expression vector, marking the first report of its expression and characterization.

Codon optimization significantly enhanced the expression levels of lumbrokinase, with the optimized version showing a fibrinolytic activity of 550,000 tPA units/L compared to 225,000 tPA units/L for the non-optimized version, highlighting the importance of genetic engineering in improving therapeutic enzyme production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Codon optimization, expression, and characterization of recombinant lumbrokinase in goat milk. Hu, R., Zhang, S., Liang, H., et al.[2006]

Lumbrokinase, derived from the earthworm Lumbricus rubellus, has been successfully purified and identified, showing strong fibrinogenolytic activity with the F85 fractions demonstrating the highest activity at 1,484.11 U/mg.

The study identified specific iso-enzymes of Lumbrokinase with distinct molecular weights, suggesting potential therapeutic applications for these enzymes in dissolving fibrin, which could be beneficial in treating conditions related to blood clots.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Purification and proteomic analysis of potent fibrinolytic enzymes extracted from Lumbricus rubellus. Stephani, L., Rahayu, P., Retnoningrum, D., et al.[2023]

Lumbrokinase (LK), an enzyme from earthworms, has been successfully expressed and purified from E. coli, showing potential as a therapeutic agent for thrombotic diseases.

In a model of thrombosis in rats, the purified recombinant LK (rLK) demonstrated effectiveness in improving thrombotic conditions, indicating its potential efficacy in treating related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression, purification, and characterization of recombinant lumbrokinase PI239 in Escherichia coli. Xu, ZR., Yang, YM., Gui, QF., et al.[2009]

Lumbrokinase, extracted from the earthworm Eisenia andrei, demonstrates dose- and time-dependent intestinal absorption when administered orally, as shown in rat studies using everted gut sacs.

The study confirmed that lumbrokinase proteins are absorbed into the bloodstream, indicating its potential as an effective oral fibrinolytic and proteolytic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal Absorption of Fibrinolytic and Proteolytic Lumbrokinase Extracted from Earthworm, Eisenia andrei. Yan, XM., Kim, CH., Lee, CK., et al.[2021]

Six lumbrokinase fractions from the earthworm Lumbricus rubellus were purified, showing varying fibrinolytic activities, with the most active fractions being F6 and F2, indicating their potential as therapeutic agents for breaking down blood clots.

The study identified that these iso-enzymes activate plasminogen into plasmin, with optimal activity at 50 degrees Celsius and a wide pH range, suggesting their stability and effectiveness in diverse physiological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Purification and characterization of six fibrinolytic serine-proteases from earthworm Lumbricus rubellus. Cho, IH., Choi, ES., Lim, HG., et al.[2019]

A potent fibrinolytic enzyme, named Lumbrokinase, was extracted from the earthworm Lumbricus rubellus, showing significant activity against both plasminogen-rich and plasminogen-free fibrin plates, with an average activity of about 100 CU/g wet weight.

The enzyme is heat-stable, has a broad optimal pH range, and exhibits unique biochemical characteristics, suggesting it could be a novel therapeutic option for conditions requiring fibrinolysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Mihara, H., Sumi, H., Yoneta, T., et al.[2019]

Citations

1. polybio.org polybio.org/projects/lumbrokinase-longcovid-me-cfs-clinical-trial/

Lumbrokinase LongCOVID & ME/CFS clinical trial A clinical trial to test if the fibrinolytic enzyme Lumbrokinase improves symptoms and mitigates blood clotting issues or platelet hyperactivation

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/518137

Lumbrokinase for Adults With Long Covid, Post-treatment ... This will be a pilot multi-arm clinical trial investigating the feasibility of Lumbrokinase (LK) as an intervention in three clinical ...

3. biomedgrid.com biomedgrid.com/pdf/AJBSR.MS.ID.002528.pdf

AJBSR.MS.ID.002528.pdf The current study furthermore demonstrates the effectiveness of the Electrocide® as a 7-day treatment for Post-COVID infection. [2] A specially ...

4. impactofvitamind.com impactofvitamind.com/wp-content/uploads/2022/07/Lumbrokinase-for-Long-COVID.pdf

Lumbrokinase for Long COVID: Considering the possibilities Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. The ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11211541/

Long COVID management: a mini review of current ... This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles.

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ame2.12465

Pharmacological effects of bioactive agents in earthworm ... This review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE)