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

Sickle Cell Anemia Clinical Trial

Official title:

Phase II Trial of Arginine Butyrate for Treatment of Refractory Leg Ulcers in Sickle Cell Disease or Beta Thalassemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004412
• Other study ID #: 199/13302
• Secondary ID: BUSM-FDR001376IN
• Status: Completed
• Phase: Phase 2
• First received: October 18, 1999
• Last updated: March 18, 2015
• Start date: September 1997
• Est. completion date: February 2005

Study information

• Verified date: March 2015
• Source: Boston University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: February 2005
• Est. primary completion date: December 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Anemia
• Skin Ulcer
• Skin Ulcers
• Ulcer

Intervention

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

Other:
• Standard local care dressing
To heal leg ulcers.

Locations

Country	Name	City	State
United States	Boston University School of Medicine	Boston	Massachusetts
United States	University of Illinois College of Medicine	Chicago	Illinois
United States	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee
United States	Mount Sinai School of Medicine	New York	New York

Sponsors (6)

Lead Sponsor	Collaborator
Susan P. Perrine	Boston Medical Center, Icahn School of Medicine at Mount Sinai, Schneider Children's Medical Center, Israel, University of Illinois at Chicago, University of Tennessee Health Science Center

Country where clinical trial is conducted

United States, 

References & 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 De — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	% Ulcers Which Completely Healed in Each Group, After 3 Months	Control Arm: given option to crossover to Treatment Arm if, ulcers have not closed after 12 weeks standard local care alone.	two additional courses of 8 week cycles	No