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| ID | Type | Description | Link |
|---|---|---|---|
| BUSM-FDR001376 | Other Identifier | Food & Drug Administration | |
| IND 36,957 | Other Identifier | Food & Drug Administration |
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| Name | Class |
|---|---|
| Boston Medical Center | OTHER |
| University of Illinois at Chicago | OTHER |
| Icahn School of Medicine at Mount Sinai | OTHER |
| University of Tennessee |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Arginine Butyrate | Drug | To determine if Arginine Butyrate accelerates healing of refractory leg ulcers over Standard Local Care alone. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| % 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 |
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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
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
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| Name | Affiliation | Role |
|---|---|---|
| Douglas V. Faller | Boston University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Illinois College of Medicine | Chicago | Illinois | 60612 | United States | ||
| Boston University School of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20955402 | Result | 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. |
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Study began 1998, contacted physicians at several medical centers with patients under their care for SCD with refractory leg ulcers. Electronic materials describing the study and its sponsor were transmitted to medical centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard Local Care Dressing | Standard local care includng cleaning, saline irrigation, dressing changes only for 8 weeks twice a week. |
| FG001 | Arginine Butyrate | Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Randomized Period |
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| OTHER |
| Schneider Children's Medical Center, Israel | OTHER |
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| Standard local care dressing | Other | To heal leg ulcers. |
|
| Boston |
| Massachusetts |
| 02118 |
| United States |
| Mount Sinai School of Medicine | New York | New York | 10029 | United States |
| University of Tennessee, Memphis Cancer Center | Memphis | Tennessee | 38103 | United States |
| FG002 | 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 Allevyn Hydrophilic PU dressing (standard local care) 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. |
| COMPLETED |
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| NOT COMPLETED |
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| Crossover Period |
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard Local Care Dressing | Standard local care dressing including cleaning, saline irrigation, dressing changes only for 8 weeks twice a week. |
| BG001 | Arginine Butyrate | Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Per protocol | Posted | Number | percentage of healed ulcers | participants were followed for an average of 3 months | number of ulcers | Participants |
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| 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. | Per Protocol | Posted | Number | percentage of completely healed ulcers | two additional courses of 8 week cycles | Number of ulcers | Participants |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard Local Care Dressing | Standard local care including cleaning, saline irrigation, dressing changes only for 8 weeks twice a week. | 5 | 11 | 1 | 11 | ||
| EG001 | Arginine Butyrate | Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours. | 9 | 15 | 0 | 15 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vaso-occlusive crisis (VOC)) | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Thrombosis | Vascular disorders | Systematic Assessment |
| ||
| Septic arthritis | Infections and infestations | Non-systematic Assessment |
| ||
| Clotted Portacath | Vascular disorders | Systematic Assessment |
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| Chronic Limb Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Head & Eye Pain | Eye disorders | Non-systematic Assessment |
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| Hypotension | Vascular disorders | Systematic Assessment |
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| Bloody Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Ulcer Infection | Infections and infestations | Non-systematic Assessment |
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| Possible Celluitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Pre-existing Osteomyelitis of Left Foot | Infections and infestations | Systematic Assessment |
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| Pleural effusion and Pericardial Effusion | Cardiac disorders | Systematic Assessment |
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| Chest Pain , SOB | Cardiac disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Decreased Appetite | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Douglas V. Faller, Ph.D., M.D., Susan P. Perrine, M.D. | Boston University School of Medicine | (617) 638-5639 | sperrine@bu.edu |
| ID | Term |
|---|---|
| D012883 | Skin Ulcer |
| D000755 | Anemia, Sickle Cell |
| D012871 | Skin Diseases |
| D030342 | Genetic Diseases, Inborn |
| D006402 | Hematologic Diseases |
| D035583 | Rare Diseases |
| D017086 | beta-Thalassemia |
| ID | Term |
|---|---|
| D017437 | Skin and Connective Tissue Diseases |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D013789 | Thalassemia |
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| ID | Term |
|---|---|
| C033018 | arginine butyrate |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Israel |
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| Number of ulcers |
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