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

This study has been completed.
Sponsor:
Collaborators:
Boston Medical Center
University of Illinois at Chicago
Mount Sinai School of Medicine
University of Tennessee Health Science Center
Schneider Children's Medical Center, Israel
Information provided by (Responsible Party):
Susan P. Perrine, Boston University
ClinicalTrials.gov Identifier:
NCT00004412
First received: October 18, 1999
Last updated: March 18, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Skin Ulcers
Sickle Cell Anemia
Drug: Arginine Butyrate
Other: Standard local care dressing
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Arginine Butyrate for Treatment of Refractory Leg Ulcers in Sickle Cell Disease or Beta Thalassemia

Resource links provided by NLM:


Further study details as provided by Boston University:

Primary Outcome Measures:
  • Healing Defined as a Decrease in Ulcer Area by at Least 25% of the Initial Area [ Time Frame: participants were followed for an average of 3 months ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • % Ulcers Which Completely Healed in Each Group, After 3 Months [ Time Frame: two additional courses of 8 week cycles ] [ Designated as safety issue: No ]
    Control Arm: given option to crossover to Treatment Arm if, ulcers have not closed after 12 weeks standard local care alone.


Enrollment: 23
Study Start Date: September 1997
Study Completion Date: February 2005
Primary Completion Date: December 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other: Standard local care dressing
To heal leg ulcers.
Experimental: 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.
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.
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.
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.

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

Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004412

Locations
United States, Illinois
University of Illinois College of Medicine
Chicago, Illinois, United States, 60612
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Tennessee
University of Tennessee, Memphis Cancer Center
Memphis, Tennessee, United States, 38103
Sponsors and Collaborators
Susan P. Perrine
Boston Medical Center
University of Illinois at Chicago
Mount Sinai School of Medicine
University of Tennessee Health Science Center
Schneider Children's Medical Center, Israel
Investigators
Study Chair: Douglas V. Faller Boston University
  More Information

Publications:
Responsible Party: Susan P. Perrine, Susan P. Perrine MD, Professor, Boston University School of Medicine, Boston University
ClinicalTrials.gov Identifier: NCT00004412     History of Changes
Other Study ID Numbers: 199/13302, BUSM-FDR001376, IND 36,957
Study First Received: October 18, 1999
Results First Received: July 22, 2013
Last Updated: March 18, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Boston University:
dermatologic disorders
genetic diseases and dysmorphic syndromes
hematologic disorders
rare disease
sickle cell anemia
skin ulcers
thalassemia major

Additional relevant MeSH terms:
Anemia, Sickle Cell
Skin Ulcer
Ulcer
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Pathologic Processes
Skin Diseases
Arginine butyrate
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on April 19, 2015