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

NCT00004412 | Completed Phase 2 Results

• 3 other identifiers: 199/13302BUSM-FDR001376IND 36,957
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

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.

Conditions

Skin Ulcers; Sickle Cell Anemia

Keywords

dermatologic disorders; genetic diseases and dysmorphic syndromes; hematologic disorders; rare disease; sickle cell anemia; skin ulcers; thalassemia major

Outcome Measures

Primary Outcomes (1)

• Healing Defined as a Decrease in Ulcer Area by at Least 25% of the Initial Area

  Treatment Arm: The AB is given as an IV infusion at 500 mg/kg over 6-9 hrs. 5 days per week for 12 weeks. After 12 weeks of therapy, if he ulcer has decreased by 25% , the AB may be continued for additional 8 weeks (twice) or, until ulcer closes plus 2 weeks, additionally. Ulcers photographed, traced, and ulcer areas calculated by computerized planimetry.

  participants were followed for an average of 3 months

Secondary Outcomes (1)

• % Ulcers Which Completely Healed in Each Group, After 3 Months

  two additional courses of 8 week cycles

Study Arms (3)

Standard local care dressing

OTHER

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.

Other: Standard local care dressing

Arginine Butyrate

EXPERIMENTAL

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.

Drug: Arginine Butyrate; Other: Standard local care dressing

Crossover

OTHER

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.

Drug: Arginine Butyrate; Other: Standard local care dressing

Interventions

Arginine Butyrate DRUG

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

Arginine Butyrate; Crossover

Standard local care dressing OTHER

To heal leg ulcers.

Arginine Butyrate; Crossover; Standard local care dressing

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

Sponsors & Collaborators

• Susan P. Perrine: lead
• Boston Medical Center: collaborator
• University of Illinois at Chicago: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• University of Tennessee: collaborator
• Schneider Children's Medical Center, Israel: collaborator

Study Sites (4)

University of Illinois College of Medicine

Chicago, Illinois, 60612, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, 38103, United States

Location

Related Publications (1)

• 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.

  PMID: 20955402 RESULT

MeSH Terms

Conditions

Skin Ulcer; Anemia, Sickle Cell; Skin Diseases; Genetic Diseases, Inborn; Hematologic Diseases; Rare Diseases; beta-Thalassemia

Interventions

arginine butyrate

Condition Hierarchy (Ancestors)

Skin and Connective Tissue Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemic and Lymphatic Diseases; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thalassemia

Results Point of Contact

• Title: Douglas V. Faller, Ph.D., M.D., Susan P. Perrine, M.D.
• Organization: Boston University School of Medicine

sperrine@bu.edu

(617) 638-5639

Study Officials

• Douglas V. Faller

  Boston University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Susan P. Perrine MD, Professor, Boston University School of Medicine

Study Record Dates

• First Submitted: October 18, 1999
• First Posted: October 19, 1999
• Study Start: September 1, 1997
• Primary Completion: December 1, 2002
• Study Completion: February 1, 2005
• Last Updated: March 31, 2015
• Results First Posted: March 31, 2015

Record last verified: 2015-03

Locations

US (4)