Placenta Derived Stem Cells for Treating of Chronic Ulcers and Neuropathy

NCT06373809 | Completed Early Phase 1 DMC

• 1 other identifier: PDSC1970222
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This is an initial dose escalation safety and exploratory efficacy study to treat two groups of subjects with critically sized diabetic wounds and diabetic neuropathy using placental-derived stem cells (PDSC) transplanted by injection into soft tissues of the lower limb. Its primary objective is safety assessment and its secondary objective is determining optimum PDSC safe dose. Group 1 will receive implantation of cells in the ulcer, in the ulcer bed, and along the distal arterial vessels that supply blood to the foot. Group 2 will follow the same protocol for the foot but will have an additional dose of cells implanted in the anterior and posterior compartments of the same leg to determine the impact on peripheral neuropathy. Dose escalation and safety will be documented. Exploratory measures of efficacy include: ulcer healing, hemodynamic and anatomical effects on the arteries of the foot, and changes in the sensory perceptions of the foot.

Conditions

Diabetic Foot; Diabetic Neuropathies; Diabetic Foot Ulcer

Outcome Measures

Primary Outcomes (1)

• Foot Ulcer Healing

  Percent closure based on changes in ulcer size dimensions in square cm.

  Baseline, 3, 6, 9 and 12 months post treatment.

Secondary Outcomes (2)

• Fine Touch Sensation: Documenting diabetes-associated lower extremity pathophysiology changes.

  Baseline, 3, 6, 9 and 12 months post treatment.

• Vibration: Documenting diabetes-associated lower extremity pathophysiology changes.

  Baseline, 3, 6, 9 and 12 months post treatment.

Study Arms (2)

Foot Ulcer

EXPERIMENTAL

The intervention at the foot in group 1 will be carried out by PDSC suspension in 60cc Lactated Ringer's (LR) solution. There will be 3 sequential blocks of subjects with increasing PDSC dose: * Block 1 (4 subjects) Total dosage (30 x 10\*6 cells) * Block 2 (3 subjects) Total dosage (40 x 10\*6 cells) * Block 3 (3 subjects) Total dosage (60 x 10\*6 cells) Administration to the ipsilateral foot / ankle in group 1 is performed by four injection sites: (1) 20 cc into the wound bed, (2) 20 cc subcutaneously around the perimeter of the wound, (3) 10 cc along the tibialis posterior pathway at the ankle prior to entry into the plantar surface, and (4) 10 cc along the tibialis anterior / dorsal foot pathway from the ankle to the dorsum of the foot.

Biological: Transplantation of Placenta Derived Stem Cells

Foot Ulcer and Leg neurophathy

EXPERIMENTAL

Dosing to the leg in group 2 will be carried out by PDSC suspension of the dose in 90cc LR solution, which will be divided equally among the three compartments of the leg. There will be 3 sequential blocks of subjects with increasing PDSC dose: * Block 1 (4 subjects) Total dosage (30 x 10\*6 cells) * Block 2 (3 subjects) Total dosage (40 x 10\*6 cells) * Block 3 (3 subjects) Total dosage (60 x 10\*6 cells) Administration to the leg will be performed through a 5 mm incision in each compartment (anterior, posterior, and lateral) at a level lower than the anterior tibial tubercle plane. These incisions will allow the introduction of a liposuction cannula of 3-4 mm in diameter and 20 cc in length, with an aroma tip and a single port that will be passed distally until the limit of the compartment is reached and, from there, the PDSCs will be injected retrograde throughout the compartment.

Biological: Transplantation of Placenta Derived Stem Cells

Interventions

Transplantation of Placenta Derived Stem Cells BIOLOGICAL

Subcutaneously administered placental-derived SVF / PDSC cells in foot, ankle, and calf tissues in 20 DFU patients

Foot Ulcer; Foot Ulcer and Leg neurophathy

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• well-controlled diabetes
• unilateral wound that exceeds an area ≥ 10 cm2, present for \> 3 months
• not candidates for surgical reconstruction
• able to understand and provide informed consent
• an additional diagnosis of peripheral arteriosclerosis is allowed.

You may not qualify if:

• presence of a disease that prohibits surgical intervention
• inadequate medical control of diabetes
• smoking, substance abuse within 3 months of the onset of the study
• inability to understand or fulfill the objectives and responsibilities of the study

Sponsors & Collaborators

• Michael H Carstens: lead
• Ministerio de Salud de Nicaragua: collaborator
• Wake Forest Institute for Regenerative Medicine: collaborator

Study Sites (2)

Hospital Escuela Oscar Danilo Rosales Arguello (HEODRA)

León, León Department, 21000, Nicaragua

Location

Hospital Escuela Cesar Amador Molina

Matagalpa, 61000, Nicaragua

Location

Related Publications (13)

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• Berishvili E, Kaiser L, Cohen M, Berney T, Scholz H, Floisand Y, Mattsson J. Treatment of COVID-19 Pneumonia: the Case for Placenta-derived Cell Therapy. Stem Cell Rev Rep. 2021 Feb;17(1):63-70. doi: 10.1007/s12015-020-10004-x.

  PMID: 32696426 BACKGROUND

• Bishop PD, Feiten LE, Ouriel K, Nassoiy SP, Pavkov ML, Clair DG, Kashyap VS. Arterial calcification increases in distal arteries in patients with peripheral arterial disease. Ann Vasc Surg. 2008 Nov;22(6):799-805. doi: 10.1016/j.avsg.2008.04.008. Epub 2008 Jul 21.

  PMID: 18640812 BACKGROUND

• Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013 Jun;15(6):641-8. doi: 10.1016/j.jcyt.2013.02.006. Epub 2013 Apr 6.

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• Bura A, Planat-Benard V, Bourin P, Silvestre JS, Gross F, Grolleau JL, Saint-Lebese B, Peyrafitte JA, Fleury S, Gadelorge M, Taurand M, Dupuis-Coronas S, Leobon B, Casteilla L. Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia. Cytotherapy. 2014 Feb;16(2):245-57. doi: 10.1016/j.jcyt.2013.11.011.

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  PMID: 21726829 BACKGROUND

• Carstens MH, Correa D, Llull R, Gomez A, Turner E, Valladares S. Subcutanous reconstruction of hand dorsum for late sequelae of burn scars using stromal vascular fractions (SVF). CellR4 2015; 3; e1675.

  BACKGROUND

• Carstens MH, Gomez A, Cortes R, Turner E, Perez C, Ocon M, Correa D. Non-reconstructable peripheral vascular disease of the lower extremity in ten patients treated with adipose-derived stromal vascular fraction cells. Stem Cell Res. 2017 Jan;18:14-21. doi: 10.1016/j.scr.2016.12.001. Epub 2016 Dec 8.

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• Carstens MH, Mendieta M, Perez C, Villareal E, Garcia R. Assisted Salvage of Ischemic Fasciocutaneous Flap Using Adipose-Derived Mesenchymal Stem Cells: In-Situ Revascularization. Aesthet Surg J. 2017 Jul 1;37(suppl_3):S38-S45. doi: 10.1093/asj/sjx052.

  PMID: 29025216 BACKGROUND

• Carstens MH, Pérez M, Briceño H, Valladares S, Correa D. Treatment of late sequelae of burn scar fibrosis with adipose-derived stromal vascular fraction (SVF) cells: a case series. CellR4 2017; 5: e2404.

  BACKGROUND

MeSH Terms

Conditions

Diabetic Foot; Diabetic Neuropathies

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Design

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

Model Details: Prospective an open label

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: April 18, 2024
• Study Start: October 8, 2021
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: April 18, 2024

Record last verified: 2024-04

Locations

NI (2)