Clinical trial NCT01894594: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Sickle Cell Anemia
Chronic Kidney Disease
Metabolic Acidosis
Keywords: Sickle cell disease
Chronic kidney disease
Bicarbonate therapy
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
First posted: 2013-07-10
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Serum bicarbonate level
timeFrame: 12 weeks
Secondary outcomes:
measure: Hemolysis markers
timeFrame: 12 weeks
Other outcomes:
measure: Tubular effect
timeFrame: 12 weeks
Locations:
city: Cleveland
country: United States
facility: University hospitals Case Medical Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Jane Little, MD
role: PRINCIPAL_INVESTIGATOR
References: