Clinical trial NCT03700580: Clinical Trial Using the Proteolytic Fraction P1G10 From V. Cundinamarcensis to Heal Diabetic Foot Ulcer
Official title: Application of a Double Blind Clinical Trial Protocol for Evaluation of Healing Action of P1G10, From V Cundinamarcensis to Chronic Neuropathic Wounds in Diabetic Foot Ulcers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Foot
Neuropathy, Diabetic
Foot Ulcer
Keywords: diabetes type 2
wound healing
peripheral neuropathy
P1G10
Lead sponsor: Federal University of Minas Gerais
Sponsor class: OTHER
First posted: 2018-10-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intervention encompassed a topical application on the ulcer bed of the active fraction 0.1% P1G10 dispersed in hydrosoluble vehicle. The control group received hydrogel with the same frequency adopted for P1G10 (Three times per week during 16 weeks). Regardless the intervention prior to each application the ulcer bed was cleaned with 0.9% physiological serum without antiseptic.
Primary purpose: TREATMENT

Brief summary: The aim of the study was to investigate the role of the proteolytic fraction from Vasconcellea cundinamarcensis, designated as P1G10, on healing of chronic foot ulcers in neuropathic patients diagnosed with diabetes type 2. Fifty patients were enrolled in a prospective, randomized, double-blind trial, to verify the efﬁcacy and safety of a topical dressing containing 0.1% P1G10, versus a Hydrogel (positive control) protocol currently applied at the Health Center to treat this condition. Upon completion of the intervention, the outcome evaluated the number of patients attaining full epithelization (100%), or at least 80% healing in both arms (P1G10 versus Hydrogel). Statistical analysis compared the endpoint data on each group to assess the signiﬁcance of differences.

Detailed description: Volunteers admitted for the study were randomly assigned into two distinct treatment groups. Randomization was performed by simple and stratified draw for each type of treatment. The treatment options were: a) Hydrogel™ and b) P1G10. The active principle had been previously dissolved in water and dispersed into Polawax dressing at 0.1% w/w final. Polawax™ is an emulsifying wax for cosmetic preparations. According to the manufacturers, it is able to hold together all types of ingredients without residue or separation. It is, therefore, ideal for "oil in water" creams and lotions. Number were used to identify both formulations.

The staff participating in this clinical trial, including researchers was unaware of the identity of the formulation applied on each proband. Each formulation used during the intervention was dispensed weekly at the Laboratory of Antitumor Substances of the Institute of Biological Sciences of the Federal University of Minas Gerais by members of the research group who had no contact with the staff responsible for the application of the protocol. The formulations were stored at 4°C until its application.

The treatment and the collection of data, took place between August 2012 and October 2016, and it was carried out by health professional and a technical assistant previously trained to evaluate and perform the procedure.

The application of the intervention was done three times per week (Monday, Wednesday and Friday), completing 48 applications or until full epithelialization of the ulcer was observed, whichever occurred first. The treatment was performed exclusively at the outpatient level. When the proband could not attend the scheduled treatment, he (she) was instructed to perform the dressing change only with 0.9% saline solution. Patients who missed two consecutive scheduled interventions were withdrawn from the study.

Ulcers were cleaned with 0.9% physiological solution using soft pressure, without scrubbing or addition of antiseptic substances. Subsequently, a thin layer of the ointment containing P1G10 or Hydrogel was applied over the ulcer bed, covering all its extension. Then double gauze was applied, fixed with adhesive tape and crepe bandage, if necessary. In cases of users with more than one wound, each wound received identical treatment, but only one ulcer was selected for the study.

During the first week of treatment, the subjects were observed for 30 minutes after the intervention, in order to verify possible undesirable effects. After this interval, if they did not present adverse events, they were released. Users were also instructed to contact the responsible investigators by telephone if they observed the emergence of any adverse effects. A prior trial of the formulation containing 0.1% P1G10 applied onto the arm of healthy individuals during one-month did not induce local or systemic affects.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of diabetes 2 had
* Hemoglobin ≥ 9.0 g/dl
* total leukocytes ≥ 300/ mm3
* platelets ≥ 100.00/mm3
* total bilirubin ≤ 1.0 mg/dL
* aspartate aminotransferase between 14 and 17 U/L in males and 10 and 33 U/L in females
* pyruvate transaminase between 10 and 40 U/L in males and 7 and 35 U/L in females
* creatinine between 0.70 and 1.20 mg/dL in males and 0.6 and 1.0 mg/dL in females

Exclusion criteria

* pregnant females
* lactating mothers
* highly exuding ulcers
* patients receiving alternative treatments for ulcers
* reported allergy to the components included in the formulation,
* concomitant uncontrolled morbidity
* current active infections,
* HIV serum positives
* diagnosed with neoplasia or undergoing treatment with a cytostatic, or immunosuppressing agent
* individuals subjected to radiotherapy within the last 3 months before beginning the trial.

Primary outcomes:
measure: 100% epithelization
timeFrame: The primary outcome (100% epithelization) is measured at the time of the intervention (1-16 weeks). If this endpoint is attained at a given date, the interval between the first intervention and the endpoint date is the period scored for the event.
Secondary outcomes:
measure: 80% epithelization
timeFrame: The secondary outcome (80% epithelization) is measured at the time of the intervention (1-16 weeks). If this endpoint is attained at a given date, the interval between the first intervention and the endpoint date is the period scored for the event.
Other outcomes:
Locations:
city: Belo Horizonte
country: Brazil
facility: Unidade de Referência Secundária (URS) Padre Eustáquio, do Distrito Sanitário Noroeste da Secretaria Municipal e Saúde de Belo Horizonte.
state: Minas Gerais
Study officials:
affiliation: Federal University of Minas Gerais
name: Miriam T Lopes, PhD
role: STUDY_DIRECTOR
References:
citation: Freitas KM, Barcelos LS, Caliari MV, Salas CE, Lopes MTP. Healing activity of proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis in a cutaneous wound excision model. Biomed Pharmacother. 2017 Dec;96:269-278. doi: 10.1016/j.biopha.2017.09.109. Epub 2017 Oct 6.
citation: Tonaco LAB, Gomes FL, Velasquez-Melendez G, Lopes MTP, Salas CE. The Proteolytic Fraction from Latex of Vasconcellea cundinamarcensis (P1G10) Enhances Wound Healing of Diabetic Foot Ulcers: A Double-Blind Randomized Pilot Study. Adv Ther. 2018 Apr;35(4):494-502. doi: 10.1007/s12325-018-0684-2. Epub 2018 Mar 21.