## Protocol Section
### Identification Module
**NCT ID:** NCT05698979

**Acronym:** BETOX

**Brief Title:** Evaluation of Botulinum TOXin Type A in the Treatment of Buerger's Disease

**Official Title:** Evaluation of Botulinum TOXin Type A in the Treatment of Buerger's Disease

#### Organization Study ID Info
**ID:** RC31/20/0445
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Toulouse
### Status Module
#### Completion Date
**Date:** 2024-06-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-07-12

**Type:** ACTUAL

**Last Update Submit Date:** 2023-07-10

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-06-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-08-30

**Type:** ESTIMATED

**Status Verified Date:** 2023-07

#### Study First Post Date
**Date:** 2023-01-26
**Type:** ACTUAL
**Study First Submit Date:** 2023-01-05
**Study First Submit QC Date:** 2023-01-16
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Toulouse

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The main objective is to assess the feasibility of treatment by injecting botulinum toxin A into the hand or foot of patients with signs of critical ischemia secondary to Buerger's disease. The injection of botulinum toxin A is carried out at the end of a single session during an hospitalization. Furthermore, tolerance and effects on the disease are evaluated at 1, 3 and 6 months post injections.

**Detailed Description:** Buerger's disease or obliterate thromboangiitis(TAO) is a rare disease. It is an inflammatory, segmental and occlusive disease affecting small and medium caliber arteries and veins in the extremities of the limbs. It mainly affects young men, who traditionally smoke, before the age of 45. There is currently no specific treatment for Buerger's disease. Surgical treatment is rarely feasible, due to distal and diffuse damage. Several studies have evaluated the perivascular injection of botulinum toxin type A (BTX) in patients with severe Raynaud syndromes linked to scleroderma, with promising results.

Studies with BTX have shown reduced pain, improved tissue perfusion with laser doppler, and healing of digital ulcers.

The patients are treated with a single session with botulinum toxin A injections during an hospital visit, and the judgmental criteria are assessed at 1, 3 and 6 months post injections.

The injections are made at 4 injection points at the palmar or distal plantar fold, at the level of the neurovascular beams, 2h after topical anesthesia by lidocaine cream under occlusion, associated or not with nitrous oxide inhaled at the time of the injections (BOTOX® 100 U, botulinum toxin A injections in each hand or foot, for a final dose of 50 U (1 ml) per extremity).

### Conditions Module

**Conditions:**

- Buerger Disease

- Raynaud Syndrome

**Keywords:**

- botulinum toxin A

- botox

- feasibility

- raynaud

- buerger

- tolerance

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 8

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Botox Injection

**Intervention Names:**

- Drug: BOTOX INJECTION

**Label:** drug administration

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- drug administration

**Description:** The patient will be treated with a single session with botulinum toxin A injections at the hospital, and the judgmental criteria will be assessed at 1, 3 and 6 months post injections.

The injections will be made in 4 injection points at the palmar or distal plantar fold, at the level of the neurovascular beams, 2h after topical anesthesia by lidocaine cream under occlusion, associated or not with nitrous oxide inhaled at the time of the injections (BOTOX® 100 U).

In the event of multiple lesions, a single limb is injected based on clinical severity (ulcer, gangrene) and ischemia parameters (lowest TCPO2).

**Name:** BOTOX INJECTION

**Other Names:**

- botulinum toxin

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The feasibility criterion corresponds to the number of patients who actually received the planned injections within the defined time limits, among the patients who should have received the injection according to the criteria of the protocol.

**Measure:** Feasibility in Number of patients

**Time Frame:** through study completion, an average of 18 months

#### Secondary Outcomes

**Description:** collection of temporary low grade adverse events (hematoma, erythema, ecchymosis at the injection site, pain, before/after and during injection)

**Measure:** tolerance of participants

**Time Frame:** during injection

**Description:** collection of temporary low grade adverse events (hematoma, erythema, ecchymosis at the injection site, pain, before/after and during injection)

**Measure:** tolerance of participants

**Time Frame:** 2 hours after injection

**Description:** collection of temporary high grade adverse events (muscle weakness, temporary or prolonged headache, general muscle weakness or muscle group at distance from injection site, difficulty swallowing, dyspnea, immediate allergic reaction to injections)

**Measure:** tolerance during injection

**Time Frame:** during injection

**Description:** collection of temporary high grade adverse events (muscle weakness, temporary or prolonged headache, general muscle weakness or muscle group at distance from injection site, difficulty swallowing, dyspnea, immediate allergic reaction to injections)

**Measure:** tolerance after injection

**Time Frame:** 2 hours after injection

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Age ≥ 18 years
2. patient with Buerger's disease according to Olin criteria (ref)
3. with digital ischemia with critical upper or lower limb ischemia criteria defined as Upper limb: pain and/or trophic disorders for at least 15 days AND digital pressure less than 50 mmHg Or TCPO2 30 mmHg) Or/and Lower limb: pain and/or trophic disorders for at least 15 days AND ankle pressure less than 50 mmHg (70 mmHg if diabetes), or 30 mmHg at the toe (50 mmHg if diabetes) or TCPO2 30 mmHg).
4. Ability to attend study visits
5. Ability to complete daily study agenda
6. Ability to give free and informed consent
7. Membership of a Social Security scheme

Exclusion Criteria:

1. History of myasthenia gravis or Eaton-Lambert syndrome
2. History of inflammatory myositis for less than 2 years or pre-existing motor neuron disease or superior limb neuropathy.
3. Known allergy to botulinum toxin or cream lidocaine, albumin or inhaled nitrous oxide/oxygen.
4. Progressive infection of one hand or foot
5. Aminoglycoside treatment
6. Pregnant or nursing women
7. History of vascular surgery of surgical sympathectomy of upper or lower limb
8. Revascularization procedure considered within 3 months of inclusion
9. Risk of major amputation within 3 months of inclusion
10. Iloprost expected within one month of study treatment
11. Hyperbaric chamber sessions scheduled within one month of study treatment
12. Life expectancy less than 6 months
13. Contraindication to one or more of the following products: BOTOX 100 UNITS ALLERGAN, LIDOCAINE/PRILOCAINE 5%, cream or NITROUS OXIDE MEDICINAL
14. Patients treated by class III anti arhythmic drugs for example amiodarone 15 ) Patient with guardians, curators, or protection of justice

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** malloizel-delaunay.j@chu-toulouse.fr

**Name:** Julie Malloizel-Delaunay, MD

**Phone:** 05 61 32 30 33

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** University Hospital, Toulouse

**Name:** Julie Malloizel-Delaunay, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### See Also Links

**Label:** Related Info

**URL:** https://www.has-sante.fr/upload/docs/application/pdf/AOMI_recos.pdf

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001157

- Term: Arterial Occlusive Diseases

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000014657

- Term: Vasculitis

- ID: D000090122

- Term: Livedoid Vasculopathy

- ID: D000013927

- Term: Thrombosis

- ID: D000016769

- Term: Embolism and Thrombosis

- ID: D000016491

- Term: Peripheral Vascular Diseases

- ID: D000017445

- Term: Skin Diseases, Vascular

- ID: D000012871

- Term: Skin Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M14772

- Name: Raynaud Disease

- Relevance: HIGH

- As Found: Raynaud's Syndrome

- ID: M16678

- Name: Thromboangiitis Obliterans

- Relevance: HIGH

- As Found: Buerger's Disease

- ID: M4465

- Name: Arterial Occlusive Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17405

- Name: Vasculitis

- Relevance: LOW

- As Found: Unknown

- ID: M2750

- Name: Livedoid Vasculopathy

- Relevance: LOW

- As Found: Unknown

- ID: M16686

- Name: Thrombosis

- Relevance: LOW

- As Found: Unknown

- ID: M7784

- Name: Embolism

- Relevance: LOW

- As Found: Unknown

- ID: M19128

- Name: Embolism and Thrombosis

- Relevance: LOW

- As Found: Unknown

- ID: M29213

- Name: Peripheral Arterial Disease

- Relevance: LOW

- As Found: Unknown

- ID: M18894

- Name: Peripheral Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M19714

- Name: Skin Diseases, Vascular

- Relevance: LOW

- As Found: Unknown

- ID: T889

- Name: Buerger Disease

- Relevance: HIGH

- As Found: Buerger's Disease

- ID: T3486

- Name: Livedoid Vasculopathy

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000013919

- Term: Thromboangiitis Obliterans

- ID: D000011928

- Term: Raynaud Disease

### Intervention Browse Module - Ancestors

- ID: D000065087

- Term: Acetylcholine Release Inhibitors

- ID: D000049990

- Term: Membrane Transport Modulators

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000018678

- Term: Cholinergic Agents

- ID: D000018377

- Term: Neurotransmitter Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: AnArAg

- Name: Anti-Arrhythmia Agents

- Abbrev: ChanBlk

- Name: Channel Blockers

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Analg

- Name: Analgesics

- Abbrev: VaDiAg

- Name: Vasodilator Agents

### Intervention Browse Module - Browse Leaves

- ID: M11014

- Name: Lidocaine

- Relevance: LOW

- As Found: Unknown

- ID: M4107

- Name: Anesthetics

- Relevance: LOW

- As Found: Unknown

- ID: M5183

- Name: Botulinum Toxins

- Relevance: HIGH

- As Found: Face

- ID: M21257

- Name: Botulinum Toxins, Type A

- Relevance: LOW

- As Found: Unknown

- ID: M250193

- Name: abobotulinumtoxinA

- Relevance: LOW

- As Found: Unknown

- ID: M12546

- Name: Nitrous Oxide

- Relevance: LOW

- As Found: Unknown

- ID: M3473

- Name: Acetylcholine

- Relevance: LOW

- As Found: Unknown

- ID: M20758

- Name: Cholinergic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000001905

- Term: Botulinum Toxins

### Misc Info Module

- Version Holder: 2024-05-24
