Efficacy, Safety Study and Benefit of Alkali Therapy in Sickle Cell Disease

Study Overview
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Brief Summary
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The objective of this study is to assess the effect of alkali administration on bicarbonate and potassium levels in patients with Sickle Cell Disease (SCD) and depressed serum bicarbonate levels. The study is a prospective non-blinded evaluation of tolerability and efficacy of alkali repletion with 4 weeks of observation and two sequential 4 week courses of escalating oral sodium bicarbonate treatment.

Detailed Description
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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.

Official Title
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Alkali Therapy in Subjects With Sickle Cell Disease (SCD) - Evaluation of Efficacy, Safety, and Beneficial Effects

Conditions
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Sickle Cell Anemia, Chronic Kidney Disease, Metabolic Acidosis

Intervention / Treatment
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* Drug: Sodium Bicarbonate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Bicarbonate<br>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: | Drug: Sodium Bicarbonate<br>* 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)<br>* Other names: Alkali Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum bicarbonate level | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle cell disease, Chronic kidney disease, Bicarbonate therapy