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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Disease; Sickle Cell Anemia; Metabolic Acidosis
• Intervention / Treatment: Drug: Sodium Bicarbonate

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: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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)

Number of Arms

1

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:

Drug: Sodium Bicarbonate; 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: Alkali Therapy

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tubular effect	To assess the influence of alkali administrations on markers of kidney tubule inflammation.	12 weeks

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Investigators: Principal Investigator: Jane Little, MD, University Hospitals Cleveland Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: July 3, 2013
• First Submitted That Met QC Criteria: July 9, 2013
• First Posted (Estimate): July 10, 2013

Study Record Updates

• Last Update Posted (Actual): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Chronic kidney disease; Sickle cell disease; Bicarbonate therapy
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Acid-Base Imbalance; Kidney Diseases; Renal Insufficiency, Chronic; Anemia, Sickle Cell; Acidosis
• Other Study ID Numbers: 09-12-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No