Clinical trial NCT00004412: Phase II Randomized Trial:Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers
Official title: Phase II Trial of Arginine Butyrate for Treatment of Refractory Leg Ulcers in Sickle Cell Disease or Beta Thalassemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Boston University
Sponsor class: OTHER
Collaborators: name: Boston Medical Center
name: University of Illinois at Chicago
name: Icahn School of Medicine at Mount Sinai
name: University of Tennessee
name: Schneider Children's Medical Center, Israel
First posted: 1999-10-19
Enrollment: 23
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: PROTOCOL CRITERIA

INCLUSION:

--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

Primary outcomes:
measure: Healing Defined as a Decrease in Ulcer Area by at Least 25% of the Initial Area
timeFrame: participants were followed for an average of 3 months
Secondary outcomes:
measure: % Ulcers Which Completely Healed in Each Group, After 3 Months
timeFrame: two additional courses of 8 week cycles
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois College of Medicine
state: Illinois
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Memphis
country: United States
facility: University of Tennessee, Memphis Cancer Center
state: Tennessee
Study officials:
affiliation: Boston University
name: Douglas V. Faller
role: STUDY_CHAIR
References:
citation: 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.