Characterization of Laboratory Response to DDAVP in Adult Hemophilia A Carriers

NCT02506023 | Completed Phase 1

• 1 other identifier: IRB00080329
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Hemophilia A

Keywords

Factor VIII antigen; von Willebrand factor (vWF) antigen; Mutation type

Outcome Measures

Primary Outcomes (1)

• 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.

  240 minutes

Secondary Outcomes (5)

• Change in the time-course response of Factor VIII antigen levels

  Baseline, 240 minutes

• Change in the time-course response of von Willebrand factor antigen (vWF:Ag) levels

  Baseline, 240 minutes

• Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of 1

  240 minutes

• Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of <1

  240 minutes

• Mean FVIII:C/vWF:Ag ratio in subjects with the baseline FVIII:C/vWF:Ag ratio of >1

  240 minutes

Study Arms (3)

Hemophilia A carriers with mild mutation

ACTIVE COMPARATOR

Hemophilia A carriers with a mild type mutation will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).

Drug: Desmopressin

Hemophilia A Carriers with severe mutation

ACTIVE COMPARATOR

Hemophilia A carriers with a severe type mutation will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).

Drug: Desmopressin

Control

ACTIVE COMPARATOR

Subjects with a mild qualitative platelet dysfunction will be given a single intravenous dose of 0.3mcg/kg of DDAVP (Desmopressin).

Drug: Desmopressin

Interventions

Desmopressin DRUG

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.

Also known as: DDAVP

Control; Hemophilia A Carriers with severe mutation; Hemophilia A carriers with mild mutation

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Children's Hospital of Atlanta Egleston

Atlanta, Georgia, 30322, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Deamino Arginine Vasopressin

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Arginine Vasopressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Robert Sidonio, Jr., MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 21, 2015
• First Posted: July 22, 2015
• Study Start: July 1, 2015
• Primary Completion: June 15, 2018
• Study Completion: June 15, 2018
• Last Updated: July 16, 2018

Record last verified: 2018-07

Locations

US (2)