Efficacy, Safety Study and Benefit of Alkali Therapy in Sickle Cell Disease
Alkali Therapy in Subjects With Sickle Cell Disease (SCD) - Evaluation of Efficacy, Safety, and Beneficial Effects
Study Overview
Status
Intervention / Treatment
Detailed Description
Primary Objective:
To assess the effect of alkali administration on bicarbonate and potassium levels in patients with SCD and depressed serum bicarbonate levels.
Secondary Objectives:
To assess the effect of alkali administration on improvement in hemolysis and on sequelae of impaired kidney function, ie, LDH, Hgb, reticulocyte count, red cell half-life, and muscle strength, Vitamin D levels, and markers of bone turnover, respectively.
To assess the influence of alkali administrations on markers of kidney tubule inflammation.
To evaluate intraparenchymal iron in patients with SCD and renal dysfunction. Safety and adverse events of alkali patients with sickle cell disease will be monitored. This research will supplement current knowledge about management of the clinically important subset of people with SCD who have renal insufficiency and acid-base perturbation.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals Case Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Sickle cell disease patients with HbSS
- eGFR <90 ml/min/1.73m2 (determined by abbreviated 4 variable modification MDRD equation) and/or measured urinary albumin to creatinine ratio >30mg/g.
- Age ≥18 years
Exclusion Criteria:
- Previous chronic treatment with alkali (including sodium bicarbonate, calcium carbonate or baking soda)
- Bicarbonate level >25 mEq/L
- Decompensated heart failure
- Uncontrolled systolic blood pressure >140 mm/Hg (the cutoff for systolic hypertension in SCD is lower than in non-SCD)
- Moderate-to-severe lower extremity edema
- Projected progression to ESRD within 6 months
- Kidney transplantation
- Treatment with immunosuppressives within the last 3 months
- Vasoocclusive (VOC) within 1 week of study entry
- Active (open) leg ulcer
- Change in hydroxyurea dose within the last 3 months, unless a self-limited interruption of a stable dose
- Blood transfusion within 8 weeks, unless on chronic transfusions
- Pregnancy
- Inability to give informed consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Sodium Bicarbonate
Patients will be monitored at baseline bi-weekly intervals for 12 weeks, the first 4 weeks to establish a stable baseline, followed by 8 weeks of alkali therapy, as follows:
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Oral sodium bicarbonate tablets administered at a starting dose of 0.6 mEQ/Kg body weight and will be escalated once, at 4 weeks, to 0.9 mEQ/Kg body weight. Weekly schedule: 0-4 weeks: Serial Measurement at baseline, without therapy 4-8 weeks: *~0.6 mEq/kg of ideal body weight of Sodium Bicarbonate tablets divided into TID dosing 8-12 weeks: *~0.9 mEq/kg of ideal body weight of Sodium Bicarbonate tablets divided into TID dosing * to the closest dose of 650 mg (7.74 mEq) Ideal Body Weight is defined by the following formulas (Devine Calculation): Ideal Body Weight (men) = 50 + 2.3 (Height (in) - 60) Ideal Body Weight (women) = 45.5 + 2.3 ( Height (in) - 60)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Serum bicarbonate level
Time Frame: 12 weeks
|
To assess the effect of alkali administration on bicarbonate and potassium levels in patients with SCD and depressed serum bicarbonate levels.
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Hemolysis markers
Time Frame: 12 weeks
|
To assess the effect of alkali administration on improvement in hemolysis and on sequelae of impaired kidney function, ie, LDH, Hgb, reticulocyte count, red cell half-life, and muscle strength, Vitamin D levels, and markers of bone turnover, respectively.
|
12 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Tubular effect
Time Frame: 12 weeks
|
To assess the influence of alkali administrations on markers of kidney tubule inflammation.
|
12 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Jane Little, MD, University Hospitals Cleveland Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 09-12-13
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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