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

• ClinicalTrials.gov Identifier: NCT01894594
• Recruitment Status: Terminated
• First Posted: July 10, 2013
• Last Update Posted: March 20, 2019
• Sponsor: University Hospitals Cleveland Medical Center
• Information provided by (Responsible Party): Jane Little, University Hospitals Cleveland Medical Center

Tracking Information

• First Submitted Date: July 3, 2013
• First Posted Date: July 10, 2013
• Last Update Posted Date: March 20, 2019
• Study Start Date: June 2013
• Actual Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 9, 2013)

Serum bicarbonate level [ Time Frame: 12 weeks ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 9, 2013)

Hemolysis markers [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: July 9, 2013)

Tubular effect [ Time Frame: 12 weeks ]

To assess the influence of alkali administrations on markers of kidney tubule inflammation.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• 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
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Sickle Cell Anemia
• Chronic Kidney Disease
• Metabolic Acidosis

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)

Other Name: Alkali Therapy

Study Arms

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:

Intervention: Drug: Sodium Bicarbonate

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 18, 2019): 7
• Original Estimated Enrollment (submitted: July 9, 2013): 20
• Actual Study Completion Date: March 2019
• Actual Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01894594
• Other Study ID Numbers: 09-12-13
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jane Little, University Hospitals Cleveland Medical Center
• Original Responsible Party: Jane Little, University Hospitals Cleveland Medical Center, Director, Sickle cell disease program
• Current Study Sponsor: University Hospitals Cleveland Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University Hospitals Cleveland Medical Center
• Verification Date: February 2018