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Proteomics and Stem Cell Therapy as a New Vascularization Strategy

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ClinicalTrials.gov Identifier: NCT02802852
Recruitment Status : Unknown
Verified June 2016 by George Havelka MD MS RPVI, University of Illinois at Chicago.
Recruitment status was:  Not yet recruiting
First Posted : June 16, 2016
Last Update Posted : June 16, 2016
Sponsor:
Information provided by (Responsible Party):
George Havelka MD MS RPVI, University of Illinois at Chicago

Brief Summary:

Neovascularization (NV) is the innate capability to enlarge collateral arteries ("arteriogenesis"), and to stimulate growth of new capillaries, arterioles and venules at the tissue level ("angiogenesis"). Patients with Chronic Limb-threatening Ischemia (CLI) present with forefoot rest-pain, ulceration and/or gangrene. They require risky and costly revascularization operations to avoid amputation. The investigators hypothesize that their inadequate NV can be modulated to restore this capability. By correcting impediments to NV in an out-patient setting, the investigators expect to facilitate CLI management.

While the following impediments to NV are complex, the solution is not. Arteriogenesis necessitates endothelial cell activation in small collaterals as blood is offloaded away from the occluded artery. Shear stress provides this stimulus, but is attenuated caudal to multi-level arterial occlusive disease. The "arteriogenesis switch" is not turned on. Furthermore, the lack of nutritive oxygenated blood inflow and the accumulation of toxic metabolic by-products are adverse to synthetic pathways in the ischemic tissue. Additionally, protein "distress" signals cannot be effectively disseminated by the ischemic tissue, and the reparative progenitor cells they are supposed to mobilize cannot effectively home back to the ischemic tissue to orchestrate NV. The CLI patient is especially disadvantaged by having diminished function and number of circulating progenitor cells (CPC). Lastly these elderly, often diabetic, patients are less able to fend off infection.

An FDA approved external programmed pneumatic compression device (PPCD) was used to restore the shear stress stimulus required for arteriogenesis. It also enhances oxygenated nutritive arterial inflow, clears waste products of metabolism (increased venous and lymphatic outflow), and helps distress proteins reach the central circulation and mobilized progenitor cells to return to the ischemic tissue. We corrected the progenitor cell and immunologic impairment with granulocyte colony stimulating factor (G-CSF), FDA approved for stem cell mobilization and immunological boost in the setting of cancer chemotherapy. The preliminary data show clinical, angiographic, hemodynamic and biochemical evidence for enhanced NV. The purpose for this study is to enroll 25 patients to reproduce the biochemical data to support a large scale clinical trial.


Condition or disease Intervention/treatment Phase
Critical Limb Ischemia Device: Pneumatic calf compression Drug: Filgrastim Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Proteomics and Stem Cell Therapy as a New Vascularization Strategy
Study Start Date : June 2016
Estimated Primary Completion Date : March 2017
Estimated Study Completion Date : March 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Calf Compression, Filgrastim injection
All patients enrolled in the study will undergo pneumatic calf compression though use of the Art Assist device as well as stem cell mobilization through administration of Filgrastim 10 mcg/kg subcutaneously, every 3rd day for 30 days.
Device: Pneumatic calf compression
Application of a pneumatic calf compression device for two hours per day, every day for 30 days.
Other Name: Art Assist Device

Drug: Filgrastim
Administration of Filgrastim 10 mcg/kg every 3rd day for 30 days
Other Name: Neupogen




Primary Outcome Measures :
  1. Hepatocyte Growth Factor [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  2. Insulin Growth Factor [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  3. Vascular Endothelial Growth Factor A [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  4. Vascular Endothelial Growth Factor B [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  5. Vascular Endothelial Growth Factor C [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  6. Vascular Endothelial Growth Factor 165b [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  7. Matrix Metalloproteinase 9 [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  8. Tissue Necrosis Factor alpha [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  9. Placental Growth Factor [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  10. Platelet Derived Growth Factor AA [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  11. Platelet Derived Growth Factor BB [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  12. Angiopoietin [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  13. Tissue Growth Factor beta [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  14. Plasmin [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  15. Fibrin Degradation Products [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  16. Interleukin 6 [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  17. Interleukin 8 [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  18. CD 34+ Cytometry [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  19. Vascular Endothelial Growth Factor Receptor 2+ Cytometry [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  20. CD 14+ Cytometry [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  21. CD 31+ Cytometry [ Time Frame: Change between 1 day, 14 days, and 30 days ]
  22. Serum Nitrate [ Time Frame: Change between 1 day, 14 days, and 30 days ]

Secondary Outcome Measures :
  1. Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) [ Time Frame: 14 days, 30 days, 6 months ]
    The generic Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) self-administered questionnaire will be completed with assistance from the PI and co-investigators at the initial visit, on Days 14 and 30 as well as at 6 months. The SF-36 covers physical and social function, and role limitations due to physical and emotional problems, mental health, energy and vitality, pain, and general health.

  2. Vascular Quality of Life Questionnaire [ Time Frame: 14 days, 30 days, 6 months ]
    The Vascular Quality of Life Questionnaire (VascuQol) self-administered questionnaire will be completed with assistance from the PI and co-investigators at the initial visit, on Days 14 and 30 as well as at 6 months. The VascuQol is a peripheral artery disease score of activity, symptom, pain, emotion, and social function.

  3. EuroQol-5D [ Time Frame: 14 days, 30 days, 6 months ]
    The EuroQol-5D self-administered questionnaire will be completed with assistance from the PI and co-investigators at the initial visit, on Days 14 and 30 as well as at 6 months. The EuroQol-5D covers mobility, self-care, usual activities, pain and discomfort, and anxiety and depression.



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Ages Eligible for Study:   35 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female between the ages of 35 and 85.
  2. Chronic limb ischemia Fontaine Class III (ischemic forefoot rest pain) and Class IV (non-healing ischemic ulcers, gangrene) with confirmatory non-invasive vascular testing.
  3. English or Spanish speaking patients

Exclusion Criteria:

  1. Acute limb ischemia requiring emergency treatment.
  2. Non-salvageable foot (e.g. extensive gangrene, advanced infection, rigor mortis, knee/hip flexion contracture, post-stroke paralysis, and hemiparesis).
  3. Untreated hypercoagulability disorder, sickle cell anemia, myeloproliferative disorder.
  4. Dialysis, and/or sustained elevated Creatinine >3.6 mg/dl.
  5. Severe dementia; bed-ridden; non-compliance; unlikely to follow-up; unreliable.
  6. Intolerance of PPCD compression
  7. Morbid obesity (Body Mass Index > 34)
  8. Severe venous insufficiency causing venous stasis ulceration and dermatitis.
  9. Uncorrected significant aorto-iliac, common femoral, and profunda femoral arterial disease
  10. Ulceration precluding PPCD placement.
  11. Active cancer.
  12. Allergy to Neupogen.
  13. Uncorrected symptomatic coronary artery disease
  14. History of lymphoma or leukemia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02802852


Contacts
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Contact: George E Havelka, MD (312) 933-0265 havelka.geo@gmail.com

Locations
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United States, Illinois
University of Illinois at Chicago Not yet recruiting
Chicago, Illinois, United States, 60612
Contact: George E Havelka, MD    312-933-0265    havelka.geo@gmail.com   
Sponsors and Collaborators
University of Illinois at Chicago
Investigators
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Principal Investigator: George E Havelka, MD University of Illinois at Chicago

Publications:
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Responsible Party: George Havelka MD MS RPVI, Assistant Professor of Surgery, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT02802852     History of Changes
Other Study ID Numbers: 2015-1244
First Posted: June 16, 2016    Key Record Dates
Last Update Posted: June 16, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Ischemia
Neovascularization, Pathologic
Pathologic Processes
Metaplasia
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs