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Characterization of Laboratory Response to DDAVP in Adult Hemophilia A Carriers

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ClinicalTrials.gov Identifier: NCT02506023
Recruitment Status : Enrolling by invitation
First Posted : July 22, 2015
Last Update Posted : May 11, 2018
Sponsor:
Information provided by (Responsible Party):
Robert Sidonio, Emory University

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

Condition or disease Intervention/treatment Phase
Hemophilia A Drug: Desmopressin Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Characterization of Laboratory Response to DDAVP in Adult Hemophilia A Carriers
Study Start Date : July 2015
Estimated Primary Completion Date : May 30, 2018
Estimated Study Completion Date : May 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arm Intervention/treatment
Active Comparator: Hemophilia A carriers with mild mutation
Hemophilia A carriers with a mild type mutation will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).
Drug: Desmopressin
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.
Other Name: DDAVP

Active Comparator: Hemophilia A Carriers with severe mutation
Hemophilia A carriers with a severe type mutation will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).
Drug: Desmopressin
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.
Other Name: DDAVP

Active Comparator: Control
Subjects with a mild qualitative platelet dysfunction will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).
Drug: Desmopressin
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.
Other Name: DDAVP




Primary Outcome Measures :
  1. Percentage of subjects that achieve and sustain >50% increase in Factor VIII antigen levels [ Time Frame: 240 minutes ]
    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 :
  1. Change in the time-course response of Factor VIII antigen levels [ Time Frame: Baseline, 240 minutes ]
    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.

  2. Change in the time-course response of von Willebrand factor antigen (vWF:Ag) levels [ Time Frame: Baseline, 240 minutes ]
    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.

  3. Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of 1 [ Time Frame: 240 minutes ]
    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.

  4. Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of <1 [ Time Frame: 240 minutes ]
    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.

  5. Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of >1 [ Time Frame: 240 minutes ]
    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.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02506023


Locations
United States, Georgia
Children's Hospital of Atlanta Egleston
Atlanta, Georgia, United States, 30322
Emory University
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Robert Sidonio, Jr., MD Emory University

Responsible Party: Robert Sidonio, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT02506023     History of Changes
Other Study ID Numbers: IRB00080329
First Posted: July 22, 2015    Key Record Dates
Last Update Posted: May 11, 2018
Last Verified: May 2018

Keywords provided by Robert Sidonio, Emory University:
Factor VIII antigen
von Willebrand factor (vWF) antigen
Mutation type

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Deamino Arginine Vasopressin
Coagulants
Hemostatics
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs