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

Primary Purpose

Sickle Cell Anemia, Chronic Kidney Disease, Metabolic Acidosis

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sodium Bicarbonate
Sponsored by
University Hospitals Cleveland Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Anemia focused on measuring Sickle cell disease, Chronic kidney disease, Bicarbonate therapy

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University hospitals Case Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sodium Bicarbonate

Arm Description

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:

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

First Posted
July 3, 2013
Last Updated
March 18, 2019
Sponsor
University Hospitals Cleveland Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01894594
Brief Title
Efficacy, Safety Study and Benefit of Alkali Therapy in Sickle Cell Disease
Official Title
Alkali Therapy in Subjects With Sickle Cell Disease (SCD) - Evaluation of Efficacy, Safety, and Beneficial Effects
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Terminated
Why Stopped
Poor recruitment
Study Start Date
June 2013 (undefined)
Primary Completion Date
March 2019 (Actual)
Study Completion Date
March 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospitals Cleveland Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Anemia, Chronic Kidney Disease, Metabolic Acidosis
Keywords
Sickle cell disease, Chronic kidney disease, Bicarbonate therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sodium Bicarbonate
Arm Type
Experimental
Arm Description
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:
Intervention Type
Drug
Intervention Name(s)
Sodium Bicarbonate
Other Intervention Name(s)
Alkali Therapy
Intervention Description
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)
Primary Outcome Measure Information:
Title
Serum bicarbonate level
Description
To assess the effect of alkali administration on bicarbonate and potassium levels in patients with SCD and depressed serum bicarbonate levels.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Hemolysis markers
Description
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.
Time Frame
12 weeks
Other Pre-specified Outcome Measures:
Title
Tubular effect
Description
To assess the influence of alkali administrations on markers of kidney tubule inflammation.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jane Little, MD
Organizational Affiliation
University Hospitals Cleveland Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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