Phase II Randomized Trial:Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers

NCT ID: NCT00004412

Last Updated: 2015-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-09-30
• Study Completion Date: 2005-02-28

Brief Summary

OBJECTIVES: I. Compare the efficacy of local care alone vs local care plus arginine butyrate in terms of healing rate in patients with refractory sickle cell ulcers.

II. Determine the effect of arginine butyrate therapy on tissue factors related to promotion or inhibition of wound healing in these patients.

III. Determine whether the regimen used in this study is appropriate for testing in pivotal trials.

Detailed Description

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive arginine butyrate IV over 6-9 hours at night 5 days a week for 12 weeks, plus concurrent standard local therapy consisting of cleaning, saline irrigation, and dressing changes as prescribed by each patient's physician. Patients who experience progressive healing receive arginine butyrate 3-4 times a week. Arginine butyrate treatment may be discontinued and reinstated following a single 2 week medical complication.

Arm II: Patients receive standard local therapy alone for 12 weeks. Patients randomized to arm II may cross over to receive arginine butyrate if no or less than 25% healing is observed after 12 weeks.

Patients whose ulcers have closed by at least 15% per cycle may receive 2 additional 8-week cycles of arginine butyrate therapy and are followed for 2 months after healing is completed.

Conditions

Skin Ulcers; Sickle Cell Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard local care dressing

Each subject provided his/her own dressing e.g,standard local care includes cleaning, saline irrigation, dressing changes only for 8 weeks twice a week.

Group Type: OTHER

Standard local care dressing

Intervention Type: OTHER

To heal leg ulcers.

Arginine Butyrate

Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 500 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 6 to 12hours.

Group Type: EXPERIMENTAL

Arginine Butyrate

Intervention Type: DRUG

To determine if Arginine Butyrate accelerates healing of refractory leg ulcers over Standard Local Care alone.

Standard local care dressing

Intervention Type: OTHER

To heal leg ulcers.

Crossover

Patients are randomly assigned (following a table of random numbers prepared by a blinded statistician) between two arms of the study. Arm I is Standard local care dressing only, and Arm II is standard local care plus Arginine Butyrate (AB), the Investigational New Drug. Ulcers observed \& traced weekly. Ulcer area calculated by computerized planimetry. After 12 weeks of therapy, if the ulcer size decreased by at least 25%, the AB may be continued for another 8 weeks (twice), or until the ulcer closes, plus an additional 2 weeks. The patients randomized to the Control Arm (standard local care) were given the option of crossing over to Arm II If, ulcers did not close after 8 weeks of standard local care.

Group Type: OTHER

Arginine Butyrate

Intervention Type: DRUG

To determine if Arginine Butyrate accelerates healing of refractory leg ulcers over Standard Local Care alone.

Standard local care dressing

Intervention Type: OTHER

To heal leg ulcers.

Interventions

Arginine Butyrate

To determine if Arginine Butyrate accelerates healing of refractory leg ulcers over Standard Local Care alone.

Intervention Type: DRUG

Standard local care dressing

To heal leg ulcers.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

--Disease Characteristics-- Significant sickle cell syndrome including Hemoglobin SS (HbSS), Hemoglobin S-beta thalassemia, and hemoglobin variants. Lower extremity or ankle ulcer (or ulcers) present for at least 6 months without healing --Patient Characteristics-- Age: 16-60 yrs Performance status: Not specified Hematopoietic: Not specified Hepatic: No hepatic compromise Transaminases no greater than 250 IU Renal: No renal compromise Creatinine no greater than 1.2 mg/mL (adults) Creatinine no greater than 0.9 mg/mL (teenagers) Other: Not pregnant Fertile patients must use effective contraception No poorly controlled seizure disorders No other secondary conditions that might inhibit immune function

• Prior/Concurrent Therapy Other: Must be treated with antibiotics prior to entry for complicating cellulitis or secondary infections

EXCLUSION :

--Prior/Concurrent Therapy-- Biologic therapy: chronic transfusion therapy Chemotherapy: prior or concurrent cancer chemotherapy concurrent butyrate derivatives Endocrine therapy: concurrent corticosteroid therapy Radiotherapy: Not specified Surgery: Not specified --Patient Characteristics-- Hepatic: hepatic compromise Transaminases greater than 250 IU Renal: renal compromise Creatinine greater than 1.2 mg/mL (adults) Creatinine greater than 0.9 mg/mL (teenagers) Other: pregnant; Fertile patients with no effective contraception Poorly controlled seizure disorders other secondary conditions that might inhibit immune function

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Medical Center

OTHER

Sponsor Role: collaborator

University of Illinois at Chicago

OTHER

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

University of Tennessee

OTHER

Sponsor Role: collaborator

Schneider Children's Medical Center, Israel

OTHER

Sponsor Role: collaborator

Susan P. Perrine

OTHER

Sponsor Role: lead

Responsible Party

Susan P. Perrine

Susan P. Perrine MD, Professor, Boston University School of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Douglas V. Faller

Role: STUDY_CHAIR

Boston University

Locations

University of Illinois College of Medicine

Chicago, Illinois, United States

Boston University School of Medicine

Boston, Massachusetts, United States

Mount Sinai School of Medicine

New York, New York, United States

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, United States

Countries

United States

References

McMahon L, Tamary H, Askin M, Adams-Graves P, Eberhardt RT, Sutton M, Wright EC, Castaneda SA, Faller DV, Perrine SP. A randomized phase II trial of Arginine Butyrate with standard local therapy in refractory sickle cell leg ulcers. Br J Haematol. 2010 Dec;151(5):516-24. doi: 10.1111/j.1365-2141.2010.08395.x. Epub 2010 Oct 19.

Reference Type: RESULT

PMID: 20955402 (View on PubMed)

Other Identifiers

BUSM-FDR001376

Identifier Type: OTHER

Identifier Source: secondary_id

IND 36,957

Identifier Type: OTHER

Identifier Source: secondary_id

199/13302

Identifier Type: -

Identifier Source: org_study_id