Intravenous Gammaglobulin for Sickle Cell Pain Crises

This is a randomized, double-blind, placebo-controlled, dose-escalation Phase I-II trial to
study the safety and efficacy of a single dose of IVIG compared to normal saline placebo
administered to patients with sickle cell anemia admitted to the hospital with an
uncomplicated acute pain episode. A total of 56 subjects will be enrolled. The hypothesis
is that IVIG will act quickly to reduce vaso-occlusion and thus pain scores, narcotic use,
and length of hospitalization. The physiological effects of IVIG in patients with sickle
cell disease will also be evaluated by measuring the adhesion receptors involved in
leukocyte adherence to endothelium and red blood cell-leukocyte interactions,
microcirculatory blood flow, and serum markers of hemolysis.

Inclusion Criteria:

- Documented diagnosis of sickle cell disease (SS or S-β thalassemia genotype)

- Age 8-65 years

- Uncomplicated acute pain episode requiring hospital admission and parenteral
narcotics

Exclusion Criteria:

- Increased stroke risk as assessed by transcranial Doppler or magnetic resonance
imaging (all subjects undergo testing)

- Concomitant acute process, including fever > 38.5° C with clinical suspicion of
infection

- Increased ALT > 2X ULN

- Serum creatinine ≥1.3 mg/dL, >300 mg/dL protein in spot urinalysis, or known
condition associated with renal dysfunction

- Hb > 10 g/dL and Hct > 30%

- IgA deficiency or known allergy to gamma globulin

- Pregnancy or breastfeeding

- Vaccination with a live attenuated virus in the preceding 6 weeks

- Documented history of illicit (eg. heroin, cocaine) drug abuse or drug-seeking
behavior

- Current participation in another investigational drug study

- Previous participation in this study within last 3 months

- Current treatment with chronic transfusion