Safety and Preliminary Efficacy of Adipose Derived Stem Cells and Low Frequency Ultrasound in PAD

NCT02756884 | Completed Early Phase 1 FDA Drug

• 1 other identifier: AHH-2015-10
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single center, open label, prospective, randomized, controlled study in patients with non- revascularizable moderate or severe lower extremity Peripheral Arterial Disease (PAD) receiving autologous stem cells therapy (minimally manipulated). This study will enroll a maximum of 10 subjects in this study. The patients will be divided into two groups. One group will receive Adipose Derived Stem Cells (ADSCs) alone and the other group will receive low frequency ultrasound before the addition of ADSCs. The randomization will be 1:1. If the results of this pilot study are not clearly different, there will be a need for a phase II study to support the results. Baseline, 6 week, 3 month and 6 month assessments of 6 min walking distance (6MWT), Ankle Brachial Indexes (ABIs)/Toe Brachial Indexes (TBIs), Transcutaneous Partial Oxygenation (TcPO2) and Rutherford assessments will be performed for the study group. Prior to the stem cell treatment, the ultrasound group patient will receive noninvasive transcutaneous pulsed focused ultrasound around the involved vessel(s) in the affected extremity. All patients will then receive 200 million autologous stromal vascular fraction cells containing adipose derived stem cell therapy: 1/3 of the cells will be delivered intra-venous proximal to the lesion (not retrograde), 1/3 of the cells will be delivered intra- adventitia proximal to the lesion and 1/3 of the cells will be delivered by intra- muscular injection along the vessel path (20-30 injections each separated by1.5 inch). Standard therapy for PAD patients will not be interrupted for the duration of the study. Standard therapy for PAD is defined as cardiovascular general measures like lifestyle changes, smoke cessation, exercise, cardiovascular rehabilitation, etc. All participants have already received maximal non-surgical therapy. Safety will be monitored on an ongoing basis.

Conditions

Peripheral Arterial Disease

Outcome Measures

Primary Outcomes (1)

• Safety measured by incidence of adverse events

  The primary outcome will be the safety/tolerability of treatment with aADSC in patients with PAD as determined by the incidence and severity of adverse events and serious adverse events.

  6 months

Secondary Outcomes (5)

• Efficacy of stem cells in improving ABI

  6 months

• Efficacy of stem cells in improving 6MWT

  6 months

• Efficacy of stem cells in improving the TcPO2

  6 months

• Efficacy of stem cells in improving Quality of Life using EQ-5D 5L questionnaire

  6 months

• Efficacy of stem cells in improving Quality of Life using the VascuQol questionnaire

  6 months

Study Arms (2)

LoFU and aADSC

EXPERIMENTAL

Low Frequency Ultrasound LFUS will be delivered in a non-sterile manner using a custom modified LFUS combined imaging/therapy probe. Adipose derived stem cells from the patient will be harvested through lipoaspiration. This solution will be injected intra-venous, intra-adventitia and intramuscular in the affected vessel and area after the administration of the low frequency ultrasound

Biological: LoFU and aADSC

Adipose Derived Stem Cells

ACTIVE COMPARATOR

Adipose derived stem cells from the patient will be harvested through lipoaspiration. This solution will be injected intra-venous, intra-adventitia and intramuscular in the affected vessel and area without the administration of the low frequency ultrasound

Biological: adipose derived stem cells

Interventions

LoFU and aADSC BIOLOGICAL

Administration of low frequency ultrasound prior to administration of autologous adipose derived stem cells.

LoFU and aADSC

adipose derived stem cells BIOLOGICAL

control arm will only received the adipose derived stem cells.

Adipose Derived Stem Cells

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and Females ≥18 years
• Patients with a Rutherford classification of 3 or 4.
• Non revascularizable lesions by balloon or stent angioplasty of the lower extremity SFA (Superficial femoral artery), Popliteal, AT (anterior tibial), PT (posterior tibial) or peroneal arteries. Non-revascularizable lesions will be determined based on a CT angiogram and/ or angiography.
• Life expectancy greater than 6 months.
• Ability to understand and provide signed informed consent.
• Reasonable expectation that patient will receive standard post-treatment care and attend all scheduled safety follow-up visits
• Written informed consent

You may not qualify if:

• Immunosuppressive agents, including but not limited to, corticosteroids and steroidal anti- inflammatory agents (SAIDS)
• Non-steroidal anti- inflammatory agents (NSAIDS)
• Patients taking currently P2Y12 inhibitors or calcium channel blockers.
• Uncontrolled seizure disorder
• Dementia
• Evidence or presence of immune deficiency.
• Presence of any other clinically-significant medical condition, psychiatric condition, or laboratory abnormality that in the judgment of the Investigator or Sponsor would pose a safety risk to the subject
• Participation in another study with an investigational drug or device within one month prior to treatment
• Females known to be pregnant, lactating or having a positive pregnancy test (will be tested during screening) or planning to become pregnant during the study
• Inability to comply with the conditions of the protocol.
• Allergy to sodium citrate or any "caine" type of local anesthetic

Sponsors & Collaborators

• Arkansas Heart Hospital: lead
• SonaCare Medical: collaborator

Study Sites (2)

Arkansas Heart Hospital

Little Rock, Arkansas, 72211, United States

Location

Arkansas Site Management Services LLC

Little Rock, Arkansas, 72211, United States

Location

Related Publications (1)

• Tebebi PA, Burks SR, Kim SJ, Williams RA, Nguyen BA, Venkatesh P, Frenkel V, Frank JA. Cyclooxygenase-2 or tumor necrosis factor-alpha inhibitors attenuate the mechanotransductive effects of pulsed focused ultrasound to suppress mesenchymal stromal cell homing to healthy and dystrophic muscle. Stem Cells. 2015 Apr;33(4):1173-86. doi: 10.1002/stem.1927.

  PMID: 25534849 BACKGROUND

MeSH Terms

Conditions

Peripheral Arterial Disease

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Study Officials

• Wilson Wong, MD

  Arkansas Heart Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2016
• First Posted: April 29, 2016
• Study Start: June 3, 2015
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: June 26, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)