Injectable Collagenase For Burns' Associated Contracture

Burn's Associated Contracture Clinical Trial

Official title:

Phase 2 Of Injectable Collagenase (Xiaflex) For Burns' Associated Contracture

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01237964
• Other study ID #: SHEBA-10-7631-JH-CTIL
• Status: Not yet recruiting
• Phase: Phase 2
• First received: November 3, 2010
• Last updated: November 9, 2010
• Start date: March 2011
• Est. completion date: August 2011

Study information

• Verified date: November 2010
• Source: Sheba Medical Center
• Contact: Joseph Haik, MD
• Phone: 972-3-5302416
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

A pilot experiment to test the efficiency of the enzyme Collagenase in treating contractures which result's from burn's healing process.

So far, treatment of choice in patients with burn's created movement limiting contractures, concentrated around supportive care. Patients were referred to surgical intervention only if necessary. Treatment by injecting an external enzyme is avant-garde and hasn't been done under such conditions.

This study might introduce a new kind of treatment, which can be done in ambulatory environment .This type of treatment might significantly improve patients' function and quality of life, with no need for a surgical intervention.

Description:

Scientific Background:

Contracture is defined as a scar tissue that replaces the original tissue and leads to shortening and tightening of the muscle results in a range of motion limitation and deformity. Contracture creation is common in burn's healing process. The process itself involves fibrosis of the effected area including intrusion towards the deep layers of the skin, and can be described as ineffective healing process. In many cases these scars have major functional and cosmetic implications that challenges the plastic surgery departments around the world.

Creation of bands, webs and contractures close to a joint area can cause a significant movement limitation and shortens the range of motion. Until recently, failure of treatment with bandaging, splints and physiotherapy activity usually led to surgical intervention involving many kinds of techniques ranging from simple incisions, Z-Plasties to skin grafts, and flaps. All these methods were meant to release the contracture itself and restore the functional capability.

A recent study showed that it's possible to use the collagenase enzyme in releasing dupuytren's contracture by a simple injection, a procedure that can be preformed under ambulatory conditions. This kind of contracture causes a fixed flexion of the fingers towards the palm of the hand. The study was a double blinded, placebo controlled study and involved 308 patients, all suffered from contracture with at least 20 degrees range of movement limitation. In the end, it was proved beyond any doubt that collagenase is effective in releasing and restoring range of motion of dupuytren's contracture. These positive results might indicate the possibility of using collagenase in other kinds of contractures.

In this study the investigators intend to perform a preliminary test of the effectiveness of collagenase in treating contracture that developed due to the burn's healing process. As comparison parameters the investigators will compare the range of motion before and after treatment and subjective feeling of pain (again, before and after treatment) according to VAS scale of pain. Also the investigators will try to monitor any kind of side effects that might appear.

In the clinical aspect, this study might introduce the medical community with a new kind of treatment protocols and even might decrease the need for surgical intervention in these patients.

Goal:

A pilot experiment to test the efficiency of the enzyme Collagenase in treating contractures which result's from burn's healing process.

Methods:

During the study the investigators will recruit about 10 patients which suffer from a known contracture that causes movement's restriction and can be attributed to burn's healing process. These patients will have to meet the exclusion and inclusion criteria of the study.

Patients will sign an informed consent in according to the Helsinki Committee, containing the list of complications and side effects expected. Patients will go through Collagenase enzyme injections according to the protocol that was conducted in the dupuytren's study. Before performing the injections, the range of motion's limitations will be measured using goniometer and a pain scale questionnaire (VAS) will be filled by the patient. Remeasuring will be done in several time periods, after the first injection, ranging from 24 hours, a week, 14 days and 28 days.

Expected results and research significance:

So far, treatment of choice in patients with burn's created movement limiting contractures, concentrated around supportive care. Patients were referred to surgical intervention only if necessary .Treatment by injecting an external enzyme is avant-garde and hasn't been done under such conditions.

Injections attempts of various enzymes such as hyaluronidase , Collagenase and also Gelatinase are documented in the literature as therapeutic trial for Keloid and hypertrophic scars in the aesthetic aspect, were found ineffective. However, literature review found no evidence of therapeutic attempts using Collagenase in burn's healing contracture for the functional aspect. These processes are known to be fibrotic and rich with collagen deposition.

This study might introduce a new kind of treatment, which can be done in ambulatory environment .This type of treatment might significantly improve patients' function and quality of life, with no need for a surgical intervention.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: August 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. age - 18+

2. Contracture is 6 month old or more

3. Place of contracture in a flex-ext joint only (e.g knee, elbow)

4. Contracture leads to 15% decrease in joint range of movement vs anatomical range

5. Physiotherapy can no longer improve those patients condition

Exclusion Criteria:

1. Any systemic condition involving skin or soft tissue disease

2. skin disease related to elastin, collagen or keratinocytes

3. Known allergy to Clostridium Collagenase enzyme

4. Psychiatric, Prisoners, Soldiers, Pregnant women

5. Patients whom due to their home location will not be available to frequent surveillance

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Burn's Associated Contracture
• Burns
• Contracture

Intervention

Drug:
• Xiaflex (FDA approved collagenase)
0.58mg of collagenase will be diluted in saline and injected in 3 points surrounding the limiting contracture

Locations

Country	Name	City	State
Israel	Sheba Hospital	Ramat Gan

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (1)

Hurst LC, Badalamente MA, Hentz VR, Hotchkiss RN, Kaplan FT, Meals RA, Smith TM, Rodzvilla J; CORD I Study Group. Injectable collagenase clostridium histolyticum for Dupuytren's contracture. N Engl J Med. 2009 Sep 3;361(10):968-79. doi: 10.1056/NEJMoa0810 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Increase functionality of involved joint	range of motion of the joint involved will be measured using Goniometer	24 hours after injection	No
Primary	Pain assessment	will be measured using VAS pain scale	24 hours after injection	No
Primary	Increase functionality of involved joint	range of motion of the joint involved will be measured using Goniometer	14 days after injection	No
Primary	Increase functionality of involved joint	range of motion of the joint involved will be measured using Goniometer	28 days after injection	No
Primary	Pain assessment	will be measured using VAS pain scale	14 days after injection	No
Primary	Pain assessment	will be measured using VAS pain scale	28 days after injection	No

External Links

•   xiaflex product which will be used during the study