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

Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01894594
• Other study ID #: 09-12-13
• Status: Terminated
• Phase: Phase 1
• Start date: June 2013
• Est. completion date: March 2019

Study information

• Verified date: February 2018
• Source: University Hospitals Cleveland Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Acidosis
• Anemia, Sickle Cell
• Chronic Kidney Disease
• Kidney Diseases
• Metabolic Acidosis
• Renal Insufficiency, Chronic
• Sickle Cell Anemia

Intervention

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)

Locations

Country	Name	City	State
United States	University hospitals Case Medical Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
University Hospitals Cleveland Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tubular effect	To assess the influence of alkali administrations on markers of kidney tubule inflammation.	12 weeks
Primary	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	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