Safety and Preliminary Efficacy of Adipose Derived Stem Cells and Low Frequency Ultrasound in PAD
Condition: Peripheral Arterial Disease
MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases
Study type: Interventional
Phase: Early Phase 1

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.
    

Detailed description: 
      This is a single center, open label, prospective, randomized, controlled study in patients
      with non- revascularizable moderate or severe lower extremity PAD receiving autologous stem
      cells therapy. We will enroll a maximum of 10 subjects in this study. The patients will be
      divided into two groups. One group will receive 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, ABIs/TBIs,
      TcPO2, 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 100 to 200 million autologous 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
      by 1.5 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.

      SUBJECT PARTICIPATION A screening evaluation to determine if a potential subject is suitable
      for participation in this trial will be conducted prior to enrollment and treatment by the
      Investigator. This includes obtaining written informed consent, collection of a complete
      medical history, including current and past medications, physical examination and clinical
      laboratory tests, PAD related testing (ABI/TBI, 6MWT, TcPO2, QoL questionnaires, etc.).

      Eligible subjects will be randomized and treated at the Sponsor hospital as approved by the
      sponsor. Study medical staff will evaluate the patients upon admission according to the
      scheduled medical assessments to ensure eligibility of the subjects. Ultrasound group will
      receive LFUS over the affected limb (see page XIV). Intra-venous, intra-adventitia and
      intramuscular dosing of the autologous ADSC will occur on the morning of Day 0. Conscious
      sedation (I.V.) may be used during the tissue harvesting and intra-adventitia administration
      of the cells.. Subjects must remain in the clinic/hospital until they are clinically stable
      for discharge; subjects that are clinically stable will be discharged into the care of a
      responsible individual. Follow-up visits will occur at 6 weeks and 3 and 6 months
      post-treatment, and may occur with the patient's personal physician who will be provided the
      follow-up assessment forms. If this occurs, the Investigator and/or Sponsor or sponsor's
      designee may also contact the patient by telephone to collect follow-up safety information.
      Adverse events, concomitant medications, vital signs, clinical laboratory test results and
      physical examinations will be collected or conducted at follow-up visits according to the
      schedule of assessments (Appendix B). All previous medical care, including medications and
      rehabilitation, for the patient's current medical conditions will be continued as prescribed
      by the patient's personal physician(s). Use of other investigational agents or treatments is
      not allowed during this study.
    

Intervention name(s): LoFU and aADSC; adipose derived stem cells
Intervention type(s): Biological; Biological
Intervention description(s): Administration of low frequency ultrasound prior to administration of autologous adipose derived stem cells.; control arm will only received the adipose derived stem cells.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment