Ignite Creation Date:
2024-05-06 @ 3:54 AM
Last Modification Date:
2024-10-26 @ 11:40 AM
Study NCT ID:
NCT02404155
Status:
COMPLETED
Last Update Posted:
2023-01-31
First Post:
2015-02-26
Brief Title:
Biomarker and Safety Study of Clozapine in Patients With Benign Ethnic Neutropenia BEN
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
Biomarker and Safety Study of Clozapine in Patients With Benign Ethnic Neutropenia BEN
Status:
COMPLETED
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BEN
Brief Summary:
Clozapine CLZ is the most effective antipsychotic for treatment-refractory schizophrenia SZ Despite the overwhelming evidence of superior efficacy CLZ is infrequently prescribed in the US at a considerably lower rate than the estimated prevalence of treatment-resistant SZ especially for African-Americans AA Recent evidence suggests that low Absolute Neutrophil Counts ANC either at baseline or during treatment are a significant barrier to CLZ use in AA patients in the US where guidelines mandate CLZ discontinuation if ANC drops below 1500 cellsmm3 The investigators group has found that discontinuation of CLZ in AA patients is over twice that in European-American EA patients N400 42 vs19 P0041 and initiation rates are 50 lower In a Statewide study N1875 the investigators reported that discontinuation was more frequently due to neutropenia in the AA sample though no AA had developed agranulocytosis 8 cases in EA Benign Ethnic Neutropenia BEN in people of African ancestry including AAs identifies a group 50 of AA with low ANCs but no increased risk of agranulocytosis or infection Low baseline or in-treatment fluctuations requiring CLZ discontinuation under current prescribing guidelines are common in CLZ-treated persons with BEN In the investigators recent pilot study of N12 AA patients with BEN treatment was safely and successfully continued with CLZ despite low baseline ANC outside current guidelines Recent evidence implicates a polymorphism in the Duffy Antigen Receptor Chemokine DARC gene in the pathophysiology of BEN In homozygotes FY-- for the DARC null allele mean within-subject neutrophil counts are reduced resulting in sporadic ANC 1500 cellsmm3 in 10-15 of people with the allele In population studies the FY-- genotype is found in 001 of EAs 993 of sub-Saharan Africans SSA and 68 of AAs Further a missense DARC mutation has been reported to interact with the DARC FY-- in determining low WBC in AAs Normal patterns of week-to-week fluctuation in ANC levels in individuals of African ancestry with BEN and the DARC null genotype are not known and no published research has examined variation in ANC in African ancestry CLZ-treated SZ patients with BEN and the DARC null genotype FY-- Such data are also lacking on individuals with BEN without the DARC null genotype Conducting such research will generate genetic marker and safety data that could be used to expand access to CLZ for AA patients who otherwise are eligible to receive this superior treatment option
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None