Use Art-assist and Neupogen to Treat Chronic Limb Ischemia

NCT02408991 | Withdrawn Phase 4 DMC

• 1 other identifier: IRB14-0553
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure the concentration of cells and proteins in the patient's blood during administration of Nuopogen (Filgrastim), a medication that is FDA approved for stem cell mobilization, in combination with a programmed pneumatic compression device (PPCD) (Art-Assist Device). The Art-Assist Device is an FDA approved device that promotes blood flow in the patient's legs. A patient will be prescribed this device and this drug to help improve the poor circulation in his/her leg. The use of Nuopogen along with the Art-Assist Device has not been approved by the FDA and is considered experimental. This study is not designed to find out how well the Art-Assist Device works, nor how well the drug works in mobilizing stem cells. Instead, it is a study of how well cells lining blood vessels in calf respond to increases in shear stress, and how well the increase in the population of certain cells in the blood stream effect how the new blood vessels will form. It is important for clinical reasons, and for the purposes of this study, that the patient uses the Art-Assist Device as prescribed on a daily basis as discussed with the patient's doctor

Conditions

Lower Limb Ischemia

Keywords

Chronic lower limb ischemia; Art-Assist Device; Neupogen

Outcome Measures

Primary Outcomes (1)

• Measuring the pharmacologic increase in of CD31+ (mature endothelial cell)

  Using the FACSaria sorter. Following clot formation (30 min) each tube will be centrifuged for 15 min at 1000g and the separated serum will be stored at -20° C. Protein will be measured using Enzyme-linked immunosorbent assays (ELISA).

  4 months

Secondary Outcomes (3)

• Measureing the pharmacologic increase in CD34+(progenitor cell),

  4 months

• Measureing the pharmacologic increase in VEGFR2+ (endothelial progenitor cell)

  4 months

• Pharmacologix measurement of nitrite

  4 months

Study Arms (1)

AA and Neopogen

EXPERIMENTAL

Patient undergoes treatment with Art-assist device and Neupogen

Drug: Neupogen; Device: Art-Assist Device

Interventions

Neupogen DRUG

Neupogen is given as an injection in your skin every three days for a total of 5 doses.

Also known as: Filgrastim

AA and Neopogen

Art-Assist Device DEVICE

The programmed pneumatic compression device (PPCD) is to be worn for a minimum of three hours daily while patient is sitting down

Also known as: The programmed pneumatic compression device (PPCD)

AA and Neopogen

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between the ages of 40 and 85.
• Chronic limb ischemia Fontaine Class III (ischemic forefoot rest pain) and Class IV (non-healing ischemic ulcers, gangrene) with confirmatory non-invasive vascular testing.

You may not qualify if:

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

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (8)

• Bussolino F, Ziche M, Wang JM, Alessi D, Morbidelli L, Cremona O, Bosia A, Marchisio PC, Mantovani A. In vitro and in vivo activation of endothelial cells by colony-stimulating factors. J Clin Invest. 1991 Mar;87(3):986-95. doi: 10.1172/JCI115107.

  PMID: 1705569 BACKGROUND

• Bussolino F, Wang JM, Defilippi P, Turrini F, Sanavio F, Edgell CJ, Aglietta M, Arese P, Mantovani A. Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature. 1989 Feb 2;337(6206):471-3. doi: 10.1038/337471a0.

  PMID: 2464767 BACKGROUND

• Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999 Apr;5(4):434-8. doi: 10.1038/7434.

  PMID: 10202935 BACKGROUND

• Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997 Feb 14;275(5302):964-7. doi: 10.1126/science.275.5302.964.

  PMID: 9020076 BACKGROUND

• Semerad CL, Christopher MJ, Liu F, Short B, Simmons PJ, Winkler I, Levesque JP, Chappel J, Ross FP, Link DC. G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood. 2005 Nov 1;106(9):3020-7. doi: 10.1182/blood-2004-01-0272. Epub 2005 Jul 21.

  PMID: 16037394 BACKGROUND

• Leone AM, Rutella S, Bonanno G, Contemi AM, de Ritis DG, Giannico MB, Rebuzzi AG, Leone G, Crea F. Endogenous G-CSF and CD34+ cell mobilization after acute myocardial infarction. Int J Cardiol. 2006 Aug 10;111(2):202-8. doi: 10.1016/j.ijcard.2005.06.043. Epub 2005 Jul 26.

  PMID: 16051386 BACKGROUND

• Takai H, Miyoshi A, Yamazaki M, Adachi K, Katagiri K, Arakawa H, Katsuyama K, Ito T, Fujii E, Hayashi S, Kato A, Suzuki M. Granulocyte colony-stimulating factor has no adverse effects on atherosclerotic lesions in high cholesterol-fed miniature Swine. J Vet Med Sci. 2008 Sep;70(9):943-50. doi: 10.1292/jvms.70.943.

  PMID: 18840969 BACKGROUND

• Cavallaro AM, Lilleby K, Majolino I, Storb R, Appelbaum FR, Rowley SD, Bensinger WI. Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor. Bone Marrow Transplant. 2000 Jan;25(1):85-9. doi: 10.1038/sj.bmt.1702072.

  PMID: 10654020 BACKGROUND

MeSH Terms

Interventions

Filgrastim

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Darwin Eton, MD

  Univ of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2015
• First Posted: April 6, 2015
• Study Start: September 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: April 8, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)