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

Primary Purpose

Skin Ulcers, Sickle Cell Anemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Arginine Butyrate
Standard local care dressing
Sponsored by
Susan P. Perrine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Skin Ulcers focused on measuring dermatologic disorders, genetic diseases and dysmorphic syndromes, hematologic disorders, rare disease, sickle cell anemia, skin ulcers, thalassemia major

Eligibility Criteria

16 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Illinois College of Medicine
  • Boston University School of Medicine
  • Mount Sinai School of Medicine
  • University of Tennessee, Memphis Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Experimental

Other

Arm Label

Standard local care dressing

Arginine Butyrate

Crossover

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

% 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.

Full Information

First Posted
October 18, 1999
Last Updated
March 18, 2015
Sponsor
Susan P. Perrine
Collaborators
Boston Medical Center, University of Illinois at Chicago, Icahn School of Medicine at Mount Sinai, University of Tennessee, Schneider Children's Medical Center, Israel
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1. Study Identification

Unique Protocol Identification Number
NCT00004412
Brief Title
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

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
September 1997 (undefined)
Primary Completion Date
December 2002 (Actual)
Study Completion Date
February 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Susan P. Perrine
Collaborators
Boston Medical Center, University of Illinois at Chicago, Icahn School of Medicine at Mount Sinai, University of Tennessee, Schneider Children's Medical Center, Israel

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Skin Ulcers, Sickle Cell Anemia
Keywords
dermatologic disorders, genetic diseases and dysmorphic syndromes, hematologic disorders, rare disease, sickle cell anemia, skin ulcers, thalassemia major

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard local care dressing
Arm Type
Other
Arm Description
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.
Arm Title
Arginine Butyrate
Arm Type
Experimental
Arm Description
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.
Arm Title
Crossover
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Arginine Butyrate
Intervention Description
To determine if Arginine Butyrate accelerates healing of refractory leg ulcers over Standard Local Care alone.
Intervention Type
Other
Intervention Name(s)
Standard local care dressing
Intervention Description
To heal leg ulcers.
Primary Outcome Measure Information:
Title
Healing Defined as a Decrease in Ulcer Area by at Least 25% of the Initial Area
Description
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.
Time Frame
participants were followed for an average of 3 months
Secondary Outcome Measure Information:
Title
% Ulcers Which Completely Healed in Each Group, After 3 Months
Description
Control Arm: given option to crossover to Treatment Arm if, ulcers have not closed after 12 weeks standard local care alone.
Time Frame
two additional courses of 8 week cycles

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas V. Faller
Organizational Affiliation
Boston University
Official's Role
Study Chair
Facility Information:
Facility Name
University of Illinois College of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Boston University School of Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Tennessee, Memphis Cancer Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20955402
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.
Results Reference
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Phase II Randomized Trial:Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers

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