Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT02314416 |
| Other study ID # |
611757 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
Phase 4
|
| First received |
December 8, 2014 |
| Last updated |
May 22, 2015 |
| Start date |
May 2015 |
| Est. completion date |
May 2015 |
Study information
| Verified date |
May 2015 |
| Source |
Georgia Regents University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Food and Drug Administration |
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of the study is to use a collagen matrix embedded with amniotic stem cells to
speed up the maturation and integration of the collagen matrix in the wound bed and shorten
total time needed for wound healing.
Description:
Wounds are a widespread problem all around the world. From a practical purpose, wounds are
divided in acute and chronic. Acute wound management depends on amount and type of tissue
destruction. Therefore, acute wounds could be furthermore subdivided as simple wound where
only skin is missing and complex wounds when some underlying structures are involved.
Complex wounds may require free flap if wound beds are poorly vascularized, devascularized
or underlying tissue wouldn't accept skin graft or biologically derived extracellular matrix
(BDEM). Simple wounds, on other hand, would be managed in the past by skin graft or by local
flap when feasible. These management strategies commonly result in unacceptable
aesthetically and/or functionally (e.g. contracture, unstable wound) outcomes and will often
require secondary reconstruction.
The second class of wounds is the chronic wounds. Chronic wounds occur whenever the normally
well-orchestrated reparative process does not proceed in a sequential and timely fashion
from hemostasis and inflammation, through proliferation to remodeling. The process is
necessarily complicated and can be delayed by many intrinsic and extrinsic factors along the
way (1). Acute and chronic wounds pose a significant burden to patients, healthcare
professionals, and the healthcare system, affecting more than 15.5 million patients and
costing an estimated $ 500 billion annually (2-3). Based on their pathogenesis, there are
four principle types of chronic wounds: venous ulcers, diabetic ulcers, arterial ischemic
and pressure ulcers.
1. Venous ulcers usually occur in the legs, account for the majority of wounds, and often
affecting the elderly with prior history of deep venous thrombosis (DVT). Ulcers form
eventually, when cells cannot keep with rate of degradation.
2. Diabetic ulcers are seen in diabetic patients who are developing ulcers for several
reasons. Neuropathy and micro-angiopathy are quite common, and these changes together
with a reduced immunity set up the perfect storm for tissue breakdown in the lower
extremities. Because of all these factors, exacerbated by impaired healing, even the
smallest cuts or bruises can become dangerously infected.
3. PAD, is a term that covers an array of medical problems caused by obstruction of the
large arteries in the arms or legs. In the advanced form of PAD, critical limb ischemia
(CLI) can occur, which is a leading cause of lower limb amputations. The Angiogenesis
Foundation estimates that 1.4 million people in the United States have CLI, with an
estimated 350,876 new cases diagnosed each year (2).
4. Pressure ulcers comprise the fourth major type of wounds. These typically occur in
people who are bedridden or whose mobility is severely limited. They are caused by a
loss of blood circulation that occurs when pressure on the tissue is greater than the
perfusion pressure in capillaries, thereby cutting off circulation, rendering tissue
ischemic. The combination of anesthesia and paralysis is a potent inducer of tissue
break down. Data from spinal cord units at Veterans Affairs Medical Centers show an
alarmingly high prevalence and incidence of pressure ulcers in young soldiers paralyzed
by spinal cord injuries.
Over the past decades, little improvement has been made in reducing morbidity and disability
from chronic wounds (3). The best available treatment for chronic wounds achieves only a 50%
healing rate that is often temporary, with an unacceptably high recurrence rate. Among the
many factors contributing to "stalling" of wound healing processes, impairment in the
production of cytokines by local inflammatory cells and fibroblasts and reduced angiogenesis
are crucial problems (4).
The introduction of BDEMs has improved wound care significantly over the years. The most
commonly used BDEM is a bovine derived collagen matrix. This bovine collagen matrix is a FDA
approved wound care device comprised of a porous matrix of cross-linked bovine tendon
collagen and glycosaminoglycan and a semi-permeable polysiloxane (silicone layer). The
collagen-glycosaminoglycan biodegradable matrix provides a scaffold for cellular invasion
and capillary growth (5). The use of the bovine collagen matrix can improve aesthetic and
functional outcomes in complex wounds with full thickness skin defects and exposure of
underlying structure such as muscle, tendons, vessels or nerves. Despite its clinical
benefit, a significant problem exists due to the long period required for vascularization
and regeneration, which requires 3 weeks as per the manufacturer. As a result, this not only
increases the cost of wound management but also decreases income potential and quality of
life.
As research is being advanced in the field of wound care, stem cell therapy is emerging to
be a promising approach to the treatment of both acute and chronic wounds. It is now known
that bone marrow-derived stem cells (BMSC) are multipotential stem cells capable of
differentiation into numerous cell types including fibroblast, muscle, brain, and cartilage
(6). Among the cells found in BMSCs is a group called mesenchymal stem cells (MSC). MSCs are
stromal cells that have been held in reserve with the ability to self-renew and also exhibit
multilineage differentiation. MSCs are also found in fetal and adult tissues and have been
isolated from umbilical cord, endometrial polyps, adipose tissue, and menstrual blood.
Because they are readily available to harvest from various tissues, MSCs are an attractive
choice in experimental and possible clinical applications.
Recent clinical observations and small sample size studies report accelerated healing in
difficult wounds by topical and regional applications of mononuclear cell preparations from
autologous bone marrow. In the rat model, the application of systemic and local BMSCs have
has resulted in improved wound healing through increased wound tensile strength, increased
collagen, and faster wound maturation (7). However, bone marrow harvesting is painful, at
times requires general anesthesia, and occasionally not feasible due to the debilitated
state of the patients. It is thus, extremely desirable to use off-the-shelf, commercially
available, allogeneic, mesenchymal stem cells.
NuCel (NutechMedical, Birmingham, AL USA) is a FDA approved allograft containing MSCs
derived from human amnion and amniotic fluid and is currently being used in different
clinical settings including orthopedic surgery and in neurosurgery as grafts. Amnion-derived
MSCs have been reported to have high trans-differentiation and angio-vasculogenic properties
(8). NuCel stem cells are immune privileged as the do not express major histo-compatibility
complex class II and has lower expression of MHC class I compared with adult bone marrow
derived stem cells. NuCel contains five types of collagen and fibronectin which are factors
involved in the wound healing process. Moreover, they are less ethically controversial due
to the abundance of waste placenta.
Multiple studies have shown that pluripotent stem cells can increase and speed up
vascularization of BDEM and significantly decrease the time to BDEM maturation (6-8). As a
result, there is potential for this application to decrease the cost of wound management and
increase quality of life.
In summary, we propose to test definitively, the safety and effectiveness of just such
allogeneic MSCs, NuCel, in promoting the healing of acute and chronic wounds. NuCel consists
of a special class of human stem cells that have the ability to express a range of
therapeutically relevant proteins and other factors, as well as form multiple cell types. We
propose a pilot study is to be conducted at the Georgia Regents University. It is a
prospective, randomized, controlled trial with the aim to generate Level I and II evidence
on the effectiveness of amniotic stem cells using a collagen matrix as a carrier in
enhancing healing of wounds.
The goal and design of the current proposal is to establish a practical protocol which has
the potential to not only accelerate the translation of advances in knowledge into new
standards of care for wound management, but also is safe, FDA approved, and inexpensively
accessible to address some of the most pressing needs in today's wound healing field. The
main objective of the current proposal is to use amniotic MSC to speed up maturation and
integration of collagen matrix in the wound bed and shorten total time needed for wound
healing. This can potentially result in a saving of hundreds of millions of dollars to the
healthcare system. The outcome of this proposal will accelerate translation of greater
medical capabilities to patients using a novel, safe and creative intervention.
