Autologous Adipose-Derived Stromal Cell Delivered Via Intramuscular Injections for the Treatment of Critical Limb Ischemia

An Open-label, Non-Randomized, Patient Funded, Multi-Center Study to Assess the Safety and Effects of Autologous Adipose-Derived Stromal Cells Via Intramuscular Injections for the Treatment of Critical Limb Ischemia

This is an open-label, non-randomized, multi center, patient sponsored study of Adipose-Derived Stromal Cell (ASC) implantation via intramuscular injections in patients who have critical limb ischemia not amenable for revascularization.

The intent of this clinical study is to answer the questions: 1) Is the proposed treatment safe and 2) Is treatment effective in improving the disease pathology of patients with diagnosed critical limb ischemia ASCs will be collected from the patient's adipose-derived tissue (body fat). Using local anesthesia, Liposuction will be performed to collect the adipose tissue specimen. The adipose tissue is then transferred to the laboratory for separation of the adipose tissue derived stem cells. In addition, peripheral blood will be collected for isolation of platelet rich plasma, which are then combined with the ASC's for intramuscular injection into the lower limb.

Study Overview

• Status: Withdrawn
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Procedure: Liposuction; Other: Stem Cell Injection

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33180
      • Ageless Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ~ 18 years
• Existence of limb ischemia, with clinical presentation corresponding to Rutherford Categories 2-6 as defined in the reporting standards adopted by \ the Society of Vascular Surgeons, or corresponding to the Leriche-Fontaine Classification, stages II, III, or IV
• Patients with, ischemia and ischemic ulceration provided patient have angiographic evidence of vascular compromise and is not a candidate for revascularization
• Stable and on optimal medical management for > 60 days as follows:
• Clopidogrel/aspirin therapy or other anticoagulation therapy, cholesterol- lowering agent, and⁄or antihypertensive medication
• Hematocrit ≥ 28.0%, White Blood Cell count ≤14,000, Platelet count ≥ 50,000
• Creatinine ≤ 2.5 mg/dL, and INR ≤ 1.6 (unless taking warfarin) or PTT < 1.5× control (to avoid bleeding complications). INR values for patients taking warfarin will be corrected prior to the procedure

• Patient meets at least one of the following diagnostic criteria for the index limb:

  1. ABI<.5mmHg
  2. TcpO2 <20 mm Hg when lying down and breathing room air, if available
  3. Or, nonhealing ulcer due to local arterial compromise with no opportunity for revascularization
• At least one non-healing distal extremity ischemic ulcer as confirmed by a vascular surgeon
• Up to date on all age and gender appropriate cancer screening per American Cancer Society

Exclusion Criteria:

• Female who is pregnant or nursing, or is of childbearing potential and not using a reliable method of contraception
• Any medical problems contraindicating tumescent syringe liposuction
• Life expectancy < 6 months

• Patient determined to be nonsurgical candidate due to reasons such as

  1. High-risk medical conditions
  2. Unstable cardiac disease
  3. Stroke or transient ischemic attack leading to limitations in lower extremities or occurring within 180 days prior to the initial screening visit
  4. Severe arthritis or other musculoskeletal disorder.
• Systolic blood pressure (supine) ≤ 90 mmHg
• Resting heart rate > 100 bpm
• Poorly controlled diabetes mellitus (HgbA1c > 10%)
• Life-threatening complications of limb ischemia necessitating immediate amputation
• Uncorrected iliac artery occlusion on index side unless corrected with stent
• Extensive necrosis of the index limb or other conditions that make amputation inevitable (Rutherford Category 6)
• Active clinical infection within one week of enrollment
• Treatment with immunosuppressant drugs
• Known drug or alcohol dependence, or any other factors which will interfere with the study conduct or interpretation of the results
• Not suitable to participate in the opinion of the principal investigator
• History cancer (other than non-melanoma skin cancer or in situ cervical cancer) within five years preceding study entry
• Unwilling and/or not able to give written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stem Cell Injection; Non-Randomized	Procedure: Liposuction; Liposuction using aspiration syringe and tumescent local anesthesia; Other Names: Adipose-Derived Stem Cells; Other: Stem Cell Injection; Stem cell implantation will be performed using intramuscular injection into the affected ischemic site of interest

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events reported		6 months
Improvement from baseline in perfusion as measured by ankle-brachial index and collateral artery number	Contrast Angiography	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement from baseline in improvement or resolution of ulcer or gangrene	Visual assessment	3 months, 6 months
Limb Salvage	Assessed with doppler to measure blood flow to the affected area.	3 months and 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Quality of Life	King's College Hospital's Vascular Quality of Life Questionnaire	3 months, 6 months

Collaborators and Investigators

• Sponsor: Ageless Regenerative Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): April 1, 2017
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: March 28, 2014
• First Posted (Estimate): March 31, 2014

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 19, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Peripheral Vascular Disease; Amputation; Critical Limb Ischemia; Gangrene; Lower Limb Ulcer; Lower Limb Wound
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: ADI-US-CLIN-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED