Effect of Blood Flow by Botulinum Toxin Injection for Severe Peripheral Artery Occlusive Disease

NCT ID: NCT06878482

Last Updated: 2025-03-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-17
• Study Completion Date: 2026-03-31

Brief Summary

The purpose of this study is to investigate the effect of subcutaneous injection of botulinum toxin A on wound healing caused by lower extremity ischemia.

Detailed Description

Tissues below the calf are governed by blood flow from the anterior tibial artery, peroneal artery, and posterior tibial artery. When an ulcer occurs due to acute lower extremity ischemia, one of the three blood vessels is blocked by a blood clot, or when the blood vessel is narrowed due to perivascular inflammation, such as Buerger's disease, it occurs in a subacute or chronic form. In particular, in the case of elderly patients with ulcers or diabetic feet due to lower extremity ischemia, the symptoms are often worsened by chronic narrowing of blood vessels due to arteriosclerosis or blockage by blood clots. To treat this, prostaglandin or antithrombotic drugs are taken, and blood flow is resumed through stent surgery, but in the lower extremities, the recurrence rate is relatively high because the blood vessels are smaller than the iliac artery, femoral artery, and popliteal artery.

Botulinum toxin is known to have a positive effect on wound healing and blood flow improvement. Botulinum toxin has been published several times in papers showing its spasmolytic effect by participating in the radiographic hip osteoarthritis Ras homolog A (RhoA)/Rock-assisted protein kinase (ROCK) pathway. In addition, botulinum toxin has a vasodilating effect related to the calcitonin gene-related peptide (CGRP) pathway, and is involved in increasing vascular endothelial growth factor (VEGF) from NO-mediated angiogenesis, inhibiting vasoconstriction, increasing blood flow rate, and promoting angiogenesis.

In this study, in patients with chronic wounds on the feet, whose lower extremity blood vessels circulate mainly through collateral circulation, subcutaneous injection of Botulinum toxin in and around the wound improves blood flow around the wound and confirms the degree of wound healing.

Conditions

Chronic Ulcer of Lower Extremity; Wound; Botulinum Toxins, Type A; Blood Circulation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Botulinum toxin A

Single group(Botulinum toxin A) Open label

Group Type: EXPERIMENTAL

Botulinum toxin A

Intervention Type: DRUG

subcutaneous injection of Botulinum toxin A

Interventions

Botulinum toxin A

subcutaneous injection of Botulinum toxin A

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 20 years old

2. Patients who have a lower extremity wound among those who have been diagnosed with moderate or severe lower extremity ischemia

3. Patients who are unable to perform additional procedures (angioplasty, etc.) by performing peripheral vascular examination and CT angiography

4. Wound size ≥ 1x1cm2 to ≤ 3x3cm2

5. Patients who can follow the clinical trial procedure well and abide by the visit schedule

6. Written informed consent to participate in the study after having fully understood the contents of the protocol and restrictions.

Exclusion Criteria

1. Patients with diseases that can affect neuromuscular function, such as myasthenia gravis, Eaton-Lamberton syndrome, amyotrophic lateral sclerosis, and motor neuropathy

2. Within 4 weeks before screening, aminoglycoside antibiotics, curare-like agents, or drugs that inhibit neuromuscular function (muscle relaxants, anticholinergics, benzodiazepines, benzamides, tetracyclines, Rinco Those who have taken mycin antibiotics, etc.)

3. Those taking aspirin, NSAIDs or anticoagulants within 7 days before screening

4. Those who have received botulinum toxin preparations within 3 months before screening

5. Angiography or CT angiography If one or more of the three major blood vessels in the lower extremity are open

6. Cases in which blood flow to the lower extremities can be preserved by performing balloon angioplasty even if all three major blood vessels in the lower extremity are blocked

7. Those who are currently taking steroids or immunosuppressants that affect wounds, or those who have taken them within one month of screening

8. Those who have applied injection drugs or wound coverings that help improve wounds within 1 week of screening

9. Women who are pregnant, lactating, planning to become pregnant during the clinical period, or women of childbearing age who are not using available contraceptive methods (women of childbearing age must be negative in the pregnancy test prior to injection).

10. Those who are allergic or sensitive to botulinum toxin

11. Those who have participated in another clinical trial within 30 days before screening or those who have not passed the half-life of the investigational product of the clinical trial that they participated in, whichever is longer.

12. Those who are not suitable for this clinical trial under the judgment of other investigators

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Hii Sun Jeong

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hiisun J, Dr

Role: PRINCIPAL_INVESTIGATOR

Yonsei University College of Medicine, Yongin Severance

Locations

Yongin Severance Hospital

Yongin-si, Gyeonggi-do, South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Hiisun J, Dr

Role: CONTACT

hsjeongps@yuhs.ac

823151899730

Facility Contacts

Hiisun Jeong, doctor

Role: primary

References

Roh TS, Jung BK, Yun I, Lew DH, Kim YS. Effect of botulinum toxin A on vasoconstriction and sympathetic neurotransmitters in a murine random pattern skin flap model. Wound Repair Regen. 2017 Jan;25(1):75-85. doi: 10.1111/wrr.12501. Epub 2017 Jan 5.

Reference Type: RESULT

PMID: 27997734 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

9-2023-0006

Identifier Type: -

Identifier Source: org_study_id