Download - 1362574160 dr. vijay viswanathan
Dr. Vijay Viswanathan, M.D, Ph.D., MNAMSJoint Director
Diabetes Research Centre &M. V. Hospital for Diabetes
Chennai.
WHO Collaborating Centre for Research, Education & Training in diabetes
Chronic wounds provide a more complex
challenge:
fluxes in the local non – healing wound
environment in which growth factors can quickly
become trapped
degraded by the proteolytic extracellular milieu.
[Trengove NJ et al., Wound Repair Regen 1999; 7: 442 – 452]
Certain growth factors are selectively inhibited in the
ulcer environment.
Treatment Modality
Reference No. of patients
examined
Method of trial
Method of
action
Results
Platelet – derived growth
factor – BB (Becaplermi
n)
Becaplermin 0.01% 272 Control -
236
Meta – analysis
of 4 RCT’s
Enhances granulation
tissue formation and
facilities epithelializatio
n
A significant reduction in
healing time. Significantly
more healing in wounds < 5 cm
Epidermal growth factor (EGF)
EGF – 21 Placebo -
19
RCT A potent dose –
dependent mitogen for granulation fibroblasts contributing to wound healing and
closure
Significantly faster wound closure and healing after 12 weeks of
therapy
Tsang MW et al.,
Diabetes Care 2003; 26: 1856 –
1861
RCT’s and clinical trials published on growth factors
Smiell JM et al., Wound
Repair Regen 1999; 7: 335 - 346
Epidermal growth factor belongs to:
A family of growth factors that regulate
cell proliferation
migration
differentiation through binding to receptor
kinases on target cells
Epidermal growth factor peptide induces
cellular proliferation through the EGF receptor:
EGF receptor:
Has a tyrosine kinase cytoplasmic
domain
Extracellular domain involved in EGF
binding and receptor dimerization.
Mechanism of action
Binding of EGF results in:
EGF receptor dimerization
autophosphorylation of the receptor
tyrosine phosphorylation of other proteins
Epidermal growth factor receptor activates
MAP kinase pathway
ultimately causing phosphorylation of
transcription factors such as c – Fos
to create AP – 1
ELK – 1 that contribute to proliferation
Healthy male or female patients between 18 – 65 years at the time of consent Patients with controlled diabetes mellitus having foot ulcers The target ulcer is no less than 2 cm2 and no more than 50 cm2
Patients with ABI > 0.8 Ulcers, which remain opened without healing for more than 2 – 3 weeks
A Phase III Study to Evaluate the Safety and Efficacy of Recombinant Human
Epidermal Growth Factor ( REGEN-D TM – 150 ) in Healing Diabetic foot Ulcers
Vijay Viswanathan, Sharad Pendsey, N.Sekar, G.S.R. Murthy
[ WOUNDS:,Vol.18, No.7 July 2006 ]
EXCLUSION CRITERIA
Patients with > Wagner’s grade III classification
Pregnant women and nursing mothers
Uncontrolled diabetes mellitus
Treatment with a dressing containing other growth factors or biological dressings within 30 days prior to the screening visit.
Epidermal Growth Factor : Diabetic Foot Ulcer Trial summary Total no. of patients - 57
• Group 1 (EGF) -29
• Group 2 (Control) - 28Group 1 Group 2 p valueNo. of patients 29 28
M / F 22 / 7 20 / 8Mean age (in
yrs)58 1.9 59 2.0
Ulcer size (in cm2)
13.3 ± 3.1 12.5± 2.2
No of Healed cases
at 15 weeks
25 12 < 0.01
Mean healing time (days)
56.8 ± 4.7 81± 4.4 < 0.01
Values are Mean SD
Week, w
Perc
enta
ge o
f pat
ients
cure
d by
wee
k w
282420161284
100
80
60
40
20
0
Figure-5: Efficacy of Regen-D Gel
ControlTest
Figure 5 : The healing takes place before the end of the 8th week in 50% of the patients under test; and it takes nearly 15 weeks to cure 50% of the patients under control.
Perc
enta
ge o
f pat
ient
s who
had
com
plet
e he
alin
g (in
wee
ks)
0
10
20
30
40
Condition Area
Control ControlTest
Test
% H
eale
d w
ithi
n 15
wee
ks
88%
100%
8%
66%
0 - 6 Above 6
Control : Placebo. Test: rhEGF
Comparison of placebo and rhEGF by ulcer area
Post – Marketing Survey (PMS) Study comparison with Phase III Clinical Data
0
2 0
4 0
6 0
8 0
1 00
5 10 15 20 25 30
Week (w)
Perc
enta
ge o
f pat
ient
s cur
ed b
y w
eek
(w) Cumulative percentages of curing
Control Test PMS
•65 year old female •Ulcer on the dorsum of left foot – one month duration•Size: 1 x 2.5 cms
Visit 1
• Size: 0.4 x 1.5 cms
Visit 4 (Week 3)
• Wound has healed completely
Visit 6 (Week 5)
• 65 year old male • Chronic non healing ulcer for 2 months duration over the lateral malleolus of the right foot •Size: 5 x 6.5 cms
Visit 1
• Size: 2.2 x 1 cms
Visit 6 (Week 5)
• The ulcer completely healed in 8 weeks.
• 63 year old female
• Tropic ulcer in the region of left fifth metatarsal
• Duration of the ulcer: 1 month
• Size: 2.5 x 2 cms
Visit 1
• Size: 1.3 x 1.3 cms
Visit 3 (Week 2)
• Wound measured about 0.4 x 0.3 cms.
• Totally healed in a weeks time.
Visit 5 (Week 4)
[Courtesy, Sharad Pendsey, Nagpur]
[Courtesy, Sharad Pendsey, Nagpur]
“I dressed the wound and God healed it”
Ambrose Pare