Clinical trial NCT02418676: Insulin Complexation With Hydroxypropyl-beta-cyclodextrin: Use of the Complex in Gel for Healing of Pressure Ulcers
Official title: Insulin Complexation With Hydroxypropyl-beta-cyclodextrin: Spectroscopic Evaluation of Molecular Inclusion and Use of the Complex in Gel for Healing of Pressure Ulcers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pressure Ulcer
Wound
Keywords: Human insulin
Hydroxypropyl-beta-cyclodextrin
Pressure Ulcer
Wound Healing
Gel
Lead sponsor: State University of Maringá
Sponsor class: OTHER
Collaborators: name: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
name: Financiadora de Estudos e Projetos
name: Fundação Araucária
First posted: 2015-04-16
Enrollment: 15
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The coprecipitation method was used to prepare hydroxypropyl-beta-cyclodextrin complexed with insulin (HPβCD-I) by mixing insulin with hydroxypropyl-beta-cyclodextrin (HPβCD) in the molar ratio of 1:5 with the addition of 10 mL of purified water for every 100 mg of the complex. After complete dissolution of the material, the mixture was stirred for 30 min at room temperature (25°C), then left to rest for 60 min and lyophilized.

The gel was prepared by dispersing the Carbopol 940® polymer in a known amount of purified water. Under mild heating the methylparaben (0.02%, w/v), propylparaben (0.01%, w/v) and propylene glycol were dissolved and incorporated in the dispersion of Carbopol 940® and left to rest for a period of 12h. After this time, the prepared gel was stirred and pH corrected to a range of 5.0 to 7.0 with triethanolamine. A set amount of insulin and the HPβCD-I complex were incorporated into the control gel for the preparation of other formulations.

A randomized, double-blind, prospective clinical trial was conducted from March 2013 to April 2014 at the Hospital Universitário Regional de Maringá (HUM), Paraná, Brazil, in order to determine the safety and efficacy of gel in patients hospitalized in the Intensive Care Unit.

Hyperglycemic volunteers and those with pressure ulcers other than grade II were excluded from the study. Grade II pressure ulcers were selected as they are a superficial lesion, with little tissue loss, and allow easy visualization of healing.

A letter of free and informed consent was obtained. The study was conducted with each patient for a period of 15 days.

The volunteers were divided equally into three groups A, B and C, with each group being formed by five volunteers (n=5). Group A was randomly selected for treatment with gel with HPβCD-I complex, group B for treatment with gel with insulin, and group C with the control gel.

Blood glucose tests were performed in order to assess whether the insulin complexed or otherwise with HPβCD could cause an increase in the rate of insulin in the blood in patients, leading to hypoglycemia.

An identical standardized procedure for gel placement was used for all patients. Initially, the pressure ulcer was cleaned with saline. With the aid of a paper ruler, the ulcer was measured and photographed, as the ruler included the date and the initials of the patient. After measuring, a quantity of 5 grams of gel was placed on the pressure ulcer and covered with sterile gauze and a transparent film.

The curative was changed once a day during the treatment period, unless there was leakage of fluid, contamination, or signs of infection. Every three days the pressure ulcers of all patients were measured and photographed again, resulting in a total of six measurements per patient. The photos of pressure ulcers were evaluated for measurement of pressure ulcers and any kind of irritation. At the end of this stage, the properly gathered study data was interpreted using the analysis software Mobile Wound Analyzer® (MOWA).

Data was evaluated by variance analysis (ANOVA), and means were compared with the Tukey test (p \< 0.05) using the software Statistica 8.0/2008 (Stat Soft Inc., Tulsa, USA).

Mixed model repeated measures methodology with some covariance structures was adopted for statistical analysis of the clinical trial (p \< 0.05). The Statistical Analysis System (SAS) for Windows, version 9.3 (SAS Inc., Chicago, IL) program was used for statistical analysis.


Eligibility criteria: Inclusion Criteria:

* Brazilian,
* bedridden,
* of both genders,
* aged between 45 and 75 years old, and
* diabetic or not.

Exclusion Criteria:

* hyperglycemic volunteers, and
* those with pressure ulcers other than grade II.

Primary outcomes:
measure: Efficacy Index (%EI)
timeFrame: Measured every 3 days for 15 days
Secondary outcomes:
measure: Blood Glucose Tests in Order to Assess Whether the Gel With Hydroxypropyl-beta-cyclodextrin Complexed With Insulin (HPβCD-I) or With Insulin Could Cause an Increase in the Rate of Insulin in the Blood of Patients
timeFrame: Assessed daily at 04 h, 10 h, 16 h and 22 h for 15 days
Other outcomes:
Locations:
Study officials:
affiliation: State University of Maringá
name: Graciette Matioli, Doctor
role: STUDY_DIRECTOR
References:
citation: Zhang L, Zhu W, Song L, Wang Y, Jiang H, Xian S, Ren Y. Effects of hydroxylpropyl-beta-cyclodextrin on in vitro insulin stability. Int J Mol Sci. 2009 May 6;10(5):2031-2040. doi: 10.3390/ijms10052031.
citation: Chaudhary H, Rohilla A, Rathee P, Kumar V. Optimization and formulation design of carbopol loaded Piroxicam gel using novel penetration enhancers. Int J Biol Macromol. 2013 Apr;55:246-53. doi: 10.1016/j.ijbiomac.2013.01.015. Epub 2013 Jan 31.
citation: Siritientong T, Angspatt A, Ratanavaraporn J, Aramwit P. Clinical potential of a silk sericin-releasing bioactive wound dressing for the treatment of split-thickness skin graft donor sites. Pharm Res. 2014 Jan;31(1):104-16. doi: 10.1007/s11095-013-1136-y. Epub 2013 Jul 31.