Intravenous Gammaglobulin for Sickle Cell Pain Crises

Pain Clinical Trial

Official title:

Phase 1-2 Trial of Gamunex (Intravenous Gammaglobulin) for Sickle Cell Acute Pain

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01757418
• Other study ID #: 09-06-172
• Secondary ID: FD-R-005341-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 2008
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Albert Einstein College of Medicine
• Contact: Deepa G Manwani, M.D
• Phone: 718-741-2342
• Email: dmanwani[@]montefiore.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether intravenous immune globulin is safe and effective in the acute treatment of pain crises in sickle cell disease. Funding Source: Food and Drug Administration (FDA), Office of Orphan Products Development (OOPD)

Description:

Patients will be randomized to a single dose of IVIG versus normal saline placebo during an uncomplicated pain crisis. Length of VOC and other secondary endpoints will be monitored.

Other known NCT identifiers

• NCT00644865

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

Inclusion Criteria:

• Documented diagnosis of sickle cell disease (SS or S-ß thalassemia genotype)
• Age 12-65 years for Phase 1 (Completed), 6-13.99 years for Phase 2 (Ongoing)
• 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%
• Hb< 5 g/dl
• Known 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
• Current treatment with chronic transfusion
• Prior thromboses or current estrogen use

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Pain
• Sickle Cell Disease

Intervention

Drug:
• Immune Globulin Intravenous
A single dose of intravenous immune globulin or saline placebo administered within 24 hours of hospital presentation. The maximum dose in Phase I was 800 mg/kg. The dose for Phase II is 400mg/kg.

Other:
• Normal saline
A single dose of normal saline administered within 24 hours of hospital admission for uncomplicated pain crisis.

Locations

Country	Name	City	State
United States	Montefiore Medical Center	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
Deepa Manwani

Country where clinical trial is conducted

United States, 

References & Publications (6)

Chang J, Shi PA, Chiang EY, Frenette PS. Intravenous immunoglobulins reverse acute vaso-occlusive crises in sickle cell mice through rapid inhibition of neutrophil adhesion. Blood. 2008 Jan 15;111(2):915-23. doi: 10.1182/blood-2007-04-084061. Epub 2007 Oct 11. — View Citation

Manwani D, Chen G, Carullo V, Serban S, Olowokure O, Jang J, Huggins M, Cohen HW, Billett H, Atweh GF, Frenette PS, Shi PA. Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis. Am J Hematol. 2015 May; — View Citation

Manwani D, Frenette PS. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. Blood. 2013 Dec 5;122(24):3892-8. doi: 10.1182/blood-2013-05-498311. Epub 2013 Sep 19. — View Citation

Manwani D, Xu C, Lee SK, Amatuni G, Cohen HW, Carullo V, Morrone K, Davila J, Shi PA, Ireland K, Keenan J, Frenette PS. Randomized phase 2 trial of Intravenous Gamma Globulin (IVIG) for the treatment of acute vaso-occlusive crisis in patients with sickle — View Citation

Shi PA, Manwani D, Olowokure O, Nandi V. Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease. Blood Cells Mol Dis. 2014 Dec;53(4):277-82. doi: 10.1016/j.bcmd.2014.04.001. Epub 2014 May 21. — View Citation

Turhan A, Jenab P, Bruhns P, Ravetch JV, Coller BS, Frenette PS. Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes. Blood. 2004 Mar 15;103(6):2397-400. doi: 10.1182/blood-2003-07-2209. Epub 2003 Nov 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of vaso-occlusive crisis	Length of vaso-occlusive crisis as measured from the time of presentation to the emergency room to end of VOC defined as 12 hours from the last dose of parenteral opioid analgesia for the treatment of VOC prior to hospital discharge.	Number of days from time of presentation to emergency room to end of crisis, average 4 days and maximum 30 days
Secondary	Total opioid use in equivalent of mg of IV morphine	End of VOC end of VOC defined as 12 hours from the last dose of parenteral opioid analgesia for the treatment of VOC prior to hospital discharge	From study drug infusion to end of crisis, average 4 days and maximum 30 days
Secondary	Time to end of vaso-occlusive crisis	Time to end of vaso-occlusive crisis as measured from start of study drug infusion to end of VOC end of VOC defined as 12 hours from the last dose of parenteral opioid analgesia for the treatment of VOC prior to hospital discharge	Number of days from start of study drug infusion to end of crisis, average 4 days and maximum 30 days
Secondary	In vitro adhesion assays	Activated Mac-1, Aged neutrophils	Pre and 24 hours post study drug