Back to resultsCharacterization of Laboratory Response to DDAVP in Adult Hemophilia A Carriers
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Desmopressin
Sponsored by
About this trial
This is an interventional diagnostic trial for Hemophilia A focused on measuring Factor VIII antigen, von Willebrand factor (vWF) antigen, Mutation type
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
Sites / Locations
- Children's Hospital of Atlanta Egleston
- Emory University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Hemophilia A carriers with mild mutation
Hemophilia A Carriers with severe mutation
Control
Arm Description
Hemophilia A carriers with a mild type mutation will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).
Hemophilia A carriers with a severe type mutation will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).
Subjects with a mild qualitative platelet dysfunction will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).
Outcomes
Primary Outcome Measures
Percentage of subjects that achieve and sustain >50% increase in Factor VIII antigen levels
After administration of intravenous Desmopressin (DDAVP) at 0.3mcg/kg, the percentage of subjects that achieve and sustain Factor VIII antigen (FVIII:C) levels >50% at 240 minutes as compared to baseline will be recorded. The levels of Factor VIII antigen (FVIII:C) will be measured using a one-stage assay. The laboratory response between carriers and the control group will be compared and the percentage of subjects that have greater than a 2-fold response from baseline and sustainment of Factor VIII antigen (FVIII:C) >50% at 240 minutes will be recorded. A lower percent of hemophilia A carriers who maintain levels of Factor VIII antigen (FVIII:C) >50% at 240 minutes indicates that the laboratory response and sustainment of Factor VIII antigen (FVIII:C) in response to Desmopressin (DDAVP) in adult hemophilia A carriers is reduced as compared to the control group.
Secondary Outcome Measures
Change in the time-course response of Factor VIII antigen levels
After administration of intravenous Desmopressin (DDAVP) at 0.3mcg/kg, the carriers will be stratified by the type of mutation (mild or severe). The levels of Factor VIII antigen will be measured using a one-stage assay at baseline and 240 minutes. The levels of Factor VIII antigen in hemophilia carriers with mild and severe mutations will be recorded.
Change in the time-course response of von Willebrand factor antigen (vWF:Ag) levels
After administration of intravenous Desmopressin (DDAVP) at 0.3mcg/kg, the carriers will be stratified by the type of mutation (mild or severe). The levels of von Willebrand factor antigen (vWF:Ag) will be measured using turbidometric assay at baseline and 240 minutes. The levels of von Willebrand factor antigen (vWF:Ag) in hemophilia carriers with mild and severe mutations will be recorded.
Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of 1
The sustainment of Factor VIII antigen (FVIII:C) levels in subjects with Factor VIII antigen:von Willebrand factor antigen (FVIII:C:vWF:Ag) ratio of 1will be assessed. The levels of Factor VIII antigen and von Willebrand factor antigen will be measured using a one-stage assay and turbidometric assays respectively. The subjects that have a baseline FVIII:C:vWF:Ag =1 will have their FVIII:C:vWF:Ag ratio assessed at 240 minutes.
Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of <1
The sustainment of Factor VIII antigen (FVIII:C) levels in subjects with Factor VIII antigen:von Willebrand factor antigen (FVIII:C:vWF:Ag) ratio of <1 will be assessed. The levels of Factor VIII antigen and von Willebrand factor antigen will be measured using a one-stage assay and turbidometric assays respectively. The subjects that have a baseline FVIII:C:vWF:Ag <1 will have their FVIII:C:vWF:Ag ratio assessed at 240 minutes.
Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of >1
The sustainment of Factor VIII antigen (FVIII:C) levels in subjects with Factor VIII antigen:von Willebrand factor antigen (FVIII:C:vWF:Ag) ratio of >1will be assessed. The levels of Factor VIII antigen and von Willebrand factor antigen will be measured using a one-stage assay and turbidometric assays respectively. The subjects that have a baseline FVIII:C:vWF:Ag >1 will have their FVIII:C:vWF:Ag ratio assessed at 240 minutes.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02506023
Brief Title
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
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
June 15, 2018 (Actual)
Study Completion Date
June 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
Keywords
Factor VIII antigen, von Willebrand factor (vWF) antigen, Mutation type
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hemophilia A carriers with mild mutation
Arm Type
Active Comparator
Arm Description
Hemophilia A carriers with a mild type mutation will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).
Arm Title
Hemophilia A Carriers with severe mutation
Arm Type
Active Comparator
Arm Description
Hemophilia A carriers with a severe type mutation will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Subjects with a mild qualitative platelet dysfunction will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).
Intervention Type
Drug
Intervention Name(s)
Desmopressin
Other Intervention Name(s)
DDAVP
Intervention Description
Desmopressin or DDAVP will be administered intravenously (IV) via a nontraumatic peripheral IV line at a dose of 0.3 mcg/kg over 30 minutes.
Primary Outcome Measure Information:
Title
Percentage of subjects that achieve and sustain >50% increase in Factor VIII antigen levels
Description
After administration of intravenous Desmopressin (DDAVP) at 0.3mcg/kg, the percentage of subjects that achieve and sustain Factor VIII antigen (FVIII:C) levels >50% at 240 minutes as compared to baseline will be recorded. The levels of Factor VIII antigen (FVIII:C) will be measured using a one-stage assay. The laboratory response between carriers and the control group will be compared and the percentage of subjects that have greater than a 2-fold response from baseline and sustainment of Factor VIII antigen (FVIII:C) >50% at 240 minutes will be recorded. A lower percent of hemophilia A carriers who maintain levels of Factor VIII antigen (FVIII:C) >50% at 240 minutes indicates that the laboratory response and sustainment of Factor VIII antigen (FVIII:C) in response to Desmopressin (DDAVP) in adult hemophilia A carriers is reduced as compared to the control group.
Time Frame
240 minutes
Secondary Outcome Measure Information:
Title
Change in the time-course response of Factor VIII antigen levels
Description
After administration of intravenous Desmopressin (DDAVP) at 0.3mcg/kg, the carriers will be stratified by the type of mutation (mild or severe). The levels of Factor VIII antigen will be measured using a one-stage assay at baseline and 240 minutes. The levels of Factor VIII antigen in hemophilia carriers with mild and severe mutations will be recorded.
Time Frame
Baseline, 240 minutes
Title
Change in the time-course response of von Willebrand factor antigen (vWF:Ag) levels
Description
After administration of intravenous Desmopressin (DDAVP) at 0.3mcg/kg, the carriers will be stratified by the type of mutation (mild or severe). The levels of von Willebrand factor antigen (vWF:Ag) will be measured using turbidometric assay at baseline and 240 minutes. The levels of von Willebrand factor antigen (vWF:Ag) in hemophilia carriers with mild and severe mutations will be recorded.
Time Frame
Baseline, 240 minutes
Title
Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of 1
Description
The sustainment of Factor VIII antigen (FVIII:C) levels in subjects with Factor VIII antigen:von Willebrand factor antigen (FVIII:C:vWF:Ag) ratio of 1will be assessed. The levels of Factor VIII antigen and von Willebrand factor antigen will be measured using a one-stage assay and turbidometric assays respectively. The subjects that have a baseline FVIII:C:vWF:Ag =1 will have their FVIII:C:vWF:Ag ratio assessed at 240 minutes.
Time Frame
240 minutes
Title
Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of <1
Description
The sustainment of Factor VIII antigen (FVIII:C) levels in subjects with Factor VIII antigen:von Willebrand factor antigen (FVIII:C:vWF:Ag) ratio of <1 will be assessed. The levels of Factor VIII antigen and von Willebrand factor antigen will be measured using a one-stage assay and turbidometric assays respectively. The subjects that have a baseline FVIII:C:vWF:Ag <1 will have their FVIII:C:vWF:Ag ratio assessed at 240 minutes.
Time Frame
240 minutes
Title
Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of >1
Description
The sustainment of Factor VIII antigen (FVIII:C) levels in subjects with Factor VIII antigen:von Willebrand factor antigen (FVIII:C:vWF:Ag) ratio of >1will be assessed. The levels of Factor VIII antigen and von Willebrand factor antigen will be measured using a one-stage assay and turbidometric assays respectively. The subjects that have a baseline FVIII:C:vWF:Ag >1 will have their FVIII:C:vWF:Ag ratio assessed at 240 minutes.
Time Frame
240 minutes
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Sidonio, Jr., MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Atlanta Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Characterization of Laboratory Response to DDAVP in Adult Hemophilia A Carriers
We'll reach out to this number within 24 hrs