Clinical trial NCT02506023: Characterization of Laboratory Response to DDAVP in Adult Hemophilia A Carriers
Official title: Characterization of Laboratory Response to DDAVP in Adult Hemophilia A Carriers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemophilia A
Keywords: Factor VIII antigen
von Willebrand factor (vWF) antigen
Mutation type
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2015-07-22
Enrollment: 2
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to determine how female hemophilia A carriers respond to a medication called DDAVP (Desmopressin).

Detailed description: DDAVP (Desmopressin) is commonly used in the treatment of persons with bleeding disorders such as hemophilia, von Willebrand disease, or qualitative platelet disorders to help them clot better. The investigator wants to assess the increase in the subjects' clotting factors in response to intravenous DDAVP (Desmopressin) and the levels of these internal clotting factors will be measured at different times after the medication is given. The investigator will compare the response to DDAVP (Desmopressin) in adult hemophilia A carriers to women with a diagnosis of qualitative platelet dysfunction.

Eligibility criteria: Inclusion Criteria:

Inclusion criteria for hemophilia A carriers:

* Females 18-60 years of age at time of enrollment
* Genetically verified or obligate hemophilia A carrier (mother of 2 boys with hemophilia A, daughter of a father with hemophilia A or mother of a son and another male relative with hemophilia A)
* To stratify patients by carriage of mutation type 10 hemophilia carriers of mild mutations that are predicted to lead to reduced FVIII secretion, protein stability or thrombin cleavage site interference and 10 hemophilia carriers of severe mutations that lead to predicted negative cross reactive material will be selected. Predicted FVIII function of the mutation will be verified by EAHAD (European Association for Haemophilia and Allied Disorders) Coagulant Factor Variant Database at www.eahad-db.org)
* Weight \>40kg to ensure volumes of blood to be drawn are within accepted safe range

Inclusion criteria for non-hemophilia A carriers (Females with mild qualitative platelet dysfunction):

* Females 18-60 years of age at time of enrollment
* Whole blood or platelet rich plasma lumiaggregometry consistent with reduced aggregation to at least 1 agonist on at least one occasion (excluding evidence of Glanzmanns Thrombasthenia or Bernard Soulier Syndrome) or determined by primary hematologist as having a qualitative platelet disorder
* Age-matched by 10 years to carrier enrolled
* Weight \>40kg to ensure volumes of blood to be drawn are within accepted safe range

Exclusion Criteria:

* Personal history of concomitant bleeding or clotting disorder
* Cardiac condition that requires the daily use of Aspirin or Clopidogrel
* Inability to comply with fluid restriction protocol for 24 hours following Desmopressin (DDAVP)
* Personal history of a myocardial infarction, renal or hepatic insufficiency or epilepsy

Primary outcomes:
measure: Percentage of subjects that achieve and sustain >50% increase in Factor VIII antigen levels
timeFrame: 240 minutes
Secondary outcomes:
measure: Change in the time-course response of Factor VIII antigen levels
timeFrame: Baseline, 240 minutes
measure: Change in the time-course response of von Willebrand factor antigen (vWF:Ag) levels
timeFrame: Baseline, 240 minutes
measure: Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of 1
timeFrame: 240 minutes
measure: Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of <1
timeFrame: 240 minutes
measure: Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of >1
timeFrame: 240 minutes
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Hospital of Atlanta Egleston
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Robert Sidonio, Jr., MD
role: PRINCIPAL_INVESTIGATOR
References: