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 will be a pilot multi-arm clinical trial investigating the feasibility of Lumbrokinase (LK) as an intervention in three clinical cohorts: * Long Covid (LC) * Post-treatment Lyme disease syndrome (PTLDS) * Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Will I have to stop taking my current medications?

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

Is lumbrokinase safe for human use?

The available research on lumbrokinase focuses on its ability to break down blood clots in animal models, but it does not provide specific safety data for humans. ^{1 2 3 4 5}

How is the drug Lumbrokinase unique for treating Long COVID?

Lumbrokinase is unique because it is a fibrinolytic enzyme derived from earthworms, which means it helps dissolve fibrin, a protein involved in blood clotting. This property may offer a novel approach to addressing blood clot-related issues in Long COVID, unlike other treatments that do not specifically target fibrin dissolution. ^{1 2 4 5 6}

What evidence supports the effectiveness of the drug Lumbrokinase for Long COVID?

Lumbrokinase, an enzyme from earthworms, has shown potential in breaking down blood clots in animal studies, which might help with conditions related to blood flow. While this suggests it could be useful for Long COVID, more specific research is needed to confirm its effectiveness for this condition. ^{1 2 4 5 7}

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

I have been diagnosed with an autoimmune condition.

Known allergy to earthworms

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, 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]

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]

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, 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]

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]

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]

Citations

1. Italy pubmed.ncbi.nlm.nih.gov

In vivo evaluation of lumbrokinase, a fibrinolytic enzyme extracted from Lumbricus rubellus, in a prosthetic vascular graft. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Purification and proteomic analysis of potent fibrinolytic enzymes extracted from Lumbricus rubellus. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. [2019]

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

Expression, purification, and characterization of recombinant lumbrokinase PI239 in Escherichia coli. [2009]

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

Codon optimization, expression, and characterization of recombinant lumbrokinase in goat milk. [2006]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Purification and characterization of six fibrinolytic serine-proteases from earthworm Lumbricus rubellus. [2019]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Intestinal Absorption of Fibrinolytic and Proteolytic Lumbrokinase Extracted from Earthworm, Eisenia andrei. [2021]