Botulinum Toxin Injection for Functional Popliteal Artery Entrapment Syndrome

• ClinicalTrials.gov Identifier: NCT03631966
• Recruitment Status: Withdrawn
• First Posted: August 15, 2018
• Last Update Posted: March 8, 2021
• Sponsor: Stanford University
• Information provided by (Responsible Party): Michael Fredericson, Stanford University

Study Description

Brief Summary:

Failure to adequately diagnose and treat patients with functional popliteal artery entrapment syndrome (PAES) leads to continued pain, loss of function and poor quality of life for many patients nationwide. Currently, the primary treatment for functional PAES involves muscle resection, sometimes involving large segments of muscle, which itself can lead to functional impairment. As such, a less invasive treatment for functional PAES is desirable. The focus of this work is to determine whether Botulinum toxin type A (BTX-A) injections into the gastrocnemius muscle can lessen the mechanical forces placed on the popliteal artery by the involved muscle, thereby improving symptoms caused by impaired distal blood flow.

Condition or disease	Intervention/treatment	Phase
Functional Popliteal Artery Entrapment Syndrome; Popliteal Artery Entrapment Syndrome	Drug: Dysport	Phase 2

Detailed Description:

Ten (10) patients with suspected functional popliteal artery entrapment syndrome will be recruited for this study. Dr. Michael Fredericson will recruit patients from local sports medicine clinics and sports teams. Equal men and women will be recruited, between the age of 18 and 50 years. This subcategory will reduce the potential of recruiting patients with age-related confounding causes for their symptoms.

After patients have been identified as having clinical features suggestive of PAES, confirmation of the diagnosis will involve the following in accordance with standards of care: 1) Ankle-brachial index testing with provocative maneuvers (maximal passive dorsiflexion and maximal active plantarflexion, treadmill running at a slope), 2) MRI angiography with provocative maneuvers (maximal plantar and dorsiflexion).

All patients will also complete at baseline a visual analog scale (VAS) of their pain, a lower extremity functional scale (LEFS), and lower extremity ultrasound for evaluation of gastrocnemius muscle size.

Currently, treatment of functional PAES involves surgical intervention frequently involving resection of the gastrocnemius muscle. As part of this study, BTX-A will be administered to the gastrocnemius. Patients will be informed about the indications, contraindications, and adverse events associated with BTX-A injections, and they will be informed of current standard of care options, including surgical intervention. Written consent will be obtained.

Dr. Michael Fredericson will carefully inject BTX-A (Dysport-Ipsen Inc.) into the proximal third of the medial and lateral gastrocnemius muscles of the symptomatic leg(s). Total dose per leg will be 400 units, 200 per injection site. Injections will be performed with the aid of real-time ultrasound (Sonosite, Bothwell, WA) guidance.

The premise of the intervention is that hypertrophy of the gastrocnemius muscle leads to functional entrapment of the popliteal artery at the level of the popliteal fossa with provocation maneuvers or exercise. By temporarily reducing muscle tone and promoting localized atrophy through BTX-A-induced chemodenervation, this entrapment can be relieved.

The primary outcome measures for this study will be VAS scores, LEFS scores, findings of improved blood flow on ABI with provocative maneuvers, and gastrocnemius size on ultrasound.

All patient's recruited to this study will have failed prior conservative treatment, and therefore any improvements seen in symptoms from the BTX-A injection will be considered above and beyond what was provided by conservative care. As such, each patient in this study design acts as their own case control (i.e. there is no appropriate intervention and/or placebo control group for these patients).

At 1 month, 3 months and 6 months post-injection, patients will return for clinical examination, visual analog scale (VAS) score, a lower extremity functional scale (LEFS), and lower extremity ultrasound for evaluation of gastrocnemius muscle size.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: All patient's recruited to this study will have failed prior conservative treatment, and therefore any improvements seen in symptoms from the BTX-A injection will be considered above and beyond what was provided by conservative care. As such, each patient in this study design acts as their own case control (i.e. there is no appropriate intervention and/or placebo control group for these patients).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Can Botulinum Toxin Injection Relieve Pain and Improve Function in Patients With Functional Popliteal Artery Entrapment Syndrome?
• Estimated Study Start Date: October 1, 2019
• Estimated Primary Completion Date: December 31, 2019
• Estimated Study Completion Date: December 31, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: BTX-A injection	Drug: Dysport; BTX-A (Dysport-Ipsen Inc.) will be injected into the proximal third of the medial and lateral gastrocnemius muscles of the symptomatic leg(s). Total dose per leg will be 400 units, 200 per injection site. Injections will be performed with the aid of real-time ultrasound (Sonosite, Bothwell, WA) guidance.

Outcome Measures

Primary Outcome Measures :

1. VAS scores [ Time Frame: 12 weeks ]
   Visual analog scale scores
2. Lower extremity functional scale scores [ Time Frame: 12 weeks ]
   A patient-reported measure of 20 items used to evaluate the functional status in the presence of lower extremity musculoskeletal disorders

Secondary Outcome Measures :

1. VAS scores [ Time Frame: 4 weeks, 18 weeks, and 6 months ]
   Visual analog scale scores
2. Lower extremity functional scale scores [ Time Frame: 4 weeks, 18 weeks, and 6 months ]
   A patient-reported measure of 20 items used to evaluate the functional status in the presence of lower extremity musculoskeletal disorders
3. blood flow on ankle-brachial indices [ Time Frame: 4 weeks, 12 weeks, and 6 months ]
4. gastrocnemius muscle size [ Time Frame: 4 weeks, 12 weeks, and 6 months ]
   as measured on lower extremity ultrasound

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• To participate in the intervention portion of the study, patients must have a confirmed diagnosis of functional PAES.
• Patients must report ongoing leg pain during or after physical activity at the time of intervention.
• Patients must have failed prior conservative treatment and have been experiencing exertional leg pain for > 6 months.
• Patients must be between the age of 18 and 50.

Exclusion Criteria:

Any subject will be excluded from the study if he/she has any of the following:

• History of muscle/tendon ruptures to the lower extremities
• History of a neurological disease that would affect running or jogging
• History of adverse reactions to BTX-A
• Concomitant diagnosis of exertional compartment syndrome or other cause for leg pain.

Contacts and Locations

Locations

United States, California

Stanford University

Redwood City, California, United States, 94063

Sponsors and Collaborators

Stanford University

More Information

• Responsible Party: Michael Fredericson, Director, Stanford PM&R Sports Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT03631966
• Other Study ID Numbers: 40251
• First Posted: August 15, 2018
• Last Update Posted: March 8, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Popliteal Artery Entrapment Syndrome; Syndrome; Disease; Pathologic Processes; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; abobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs