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

Phase 1

Terminated

• Conditions: Metabolic Acidosis; Chronic Kidney Disease; Sickle Cell Anemia
• Interventions: Drug: Sodium Bicarbonate

• Registration Number: NCT01894594
• Lead Sponsor: University Hospitals Cleveland Medical Center

Brief Summary

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

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 Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-07-03
• Study First Submitted QC: 2013-07-09
• Study First Posted: 2013-07-10
• Status Verified: 2018-02
• Primary Completion: 2019-03
• Study Completion: 2019-03
• Last Update Submitted: 2019-03-18
• Last Update Posted: 2019-03-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sodium Bicarbonate	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:

Primary Outcome Measures

Name	Time	Method
Serum bicarbonate level	12 weeks	To assess the effect of alkali administration on bicarbonate and potassium levels in patients with SCD and depressed serum bicarbonate levels.

Secondary Outcome Measures

Name	Time	Method
Hemolysis markers	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.

Trial Locations

Locations (1)

University hospitals Case Medical Center; 🇺🇸 Cleveland, Ohio, United States