Low VW Activity in Adolescent HMB (Low VWF)

Genotypic and Phenotypic Analysis of Adolescents With Heavy Menstrual Bleeding and Low Von Willebrand Activity

This is a research study for patients diagnosed with heavy menstrual bleeding (HMB) and low Von Willebrand Factor (VWF). Menstruation, also known as a period, is the regular discharge of blood and tissues from the uterus. HMB is having a heavier amount of discharge during menstrual period. Low Von Willebrand Factor means that the participant has lower level of a blood protein that is important for clotting of blood and so, the participant is at a higher risk for bleeding.

The purpose of this project is to study the genetic differences of adolescent females with HMB and low VWF activity and compare the genetic differences with their bleeding manifestations, response to medications and outcome.

Study Overview

• Status: Active, not recruiting
• Conditions: Von Willebrand Factor Deficiency
• Intervention / Treatment: Other: Genetic Analysis; Other: Medical Record Data Abstraction; Other: Pictorial Blood Assessment Chart (PBAC) score; Other: Complete Bleeding Symptom ISTH Bleeding Assessment Tool

Detailed Description

One hundred and twenty subjects will be enrolled. Adolescent females with heavy menstrual bleeding (HMB) and low Von Willebrand Factor (VWF) will be recruited.

Data collection will occur from participant's medical records in regards to their low VWF activity and HMB medical history.

Participants will be asked to complete symptom questionnaires in regards to their HMB.

A blood sample will be collected to analyze how many participants have the disease causing sequence variation in the VWF gene and other genes affecting bleeding, clotting and blood vessel biology and correlated with their bleeding history.

The blood sample will be deidentified and stored indefinitely for future research.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Hospital of Atlanta
  • Michigan
    • East Lansing, Michigan, United States, 48823
      • Michigan State University
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Joseph M Sanzari Children's Hospital
  • New York
    • Buffalo, New York, United States, 14209
      • Hemophilia Center of Western New York
    • Rochester, New York, United States, 14621
      • Mary M. Gooley Hemophilia Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center- Children's Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Females under the age of 21 years old with heavy menstrual bleeding and low von willebrand factor

Description

Inclusion Criteria:

• Post-menarchal females less than 21 years of age
• HMB defined as PBAC score greater than 100
• VWF:Activity more than or equal to 30 and less than or equal to 50 IU/dL x 2
• VWF: Activity /VWF:Ag ratio greater than or equal to 0.6
• Normal VW multimers, if performed

Exclusion Criteria:

• Post menarchal females age greater than or equal to 21 years
• VWF: Activity less than 30 or greater than 50 IU/dL consistently, type 2 or type 3 VWD
• Presence of other bleeding disorders (thrombocytopenia, platelet function defect, coagulation factor deficiency, fibrinogen defect or deficiency)

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Group A; Adolescent women with heavy menstrual bleeding and low von willebrand factor activity.

Other: Genetic Analysis; Blood sample will be drawn to assess the number of participants enrolled that have sequence variation in the von willebrand factor gene and other genes affecting bleeding, clotting and blood vessel biology.; Other: Medical Record Data Abstraction; The subject's response to intranasal or intravenous desmopressin (DDAVP) challenge performed as part of standard of care will be recorded. The desmopressin is a drug that increases the clotting factor in blood to prevent bleeding. Medical and family history including and not limited to age, diagnoses, race/ethnicity, lab values, HMB and low VWF activity diagnoses, and treatment history and outcome will also be recorded.; Other: Pictorial Blood Assessment Chart (PBAC) score; PBAC is a pictorial tool to assess menstrual blood loss. Study team will complete the PBAC assessment with each study participant evaluating and measure response to different treatments for menstrual blood loss in the clinic setting between those with VWD versus other bleeding disorders.; Other Names: PBAC Score; Other: Complete Bleeding Symptom ISTH Bleeding Assessment Tool; Study participants will complete the ISTH BAT assessment. The ISTH BAT is a questionnaire to aid in the standardized evaluation of the presence and severity of bleeding symptoms.; Other Names: ISTH BAT Assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adolescents with Low VWF and HMB with genetic variations in VWF gene and other genes affecting bleeding, clotting and blood vessel biology	The genetic variations of adolescent females with heavy menstrual bleeding and low von Willebrand factor activity in VWF gene and other genes affecting bleeding, clotting and blood vessel biology	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adolescents with Low VWF and HMB with genetic variations and bleeding phenotype (including PBAC score and ISTH-BAT score, response to DDAVP challenge, HMB therapy)	The correlation of subjects with and without genetic variations with bleeding phenotype (including PBAC score, ISTH BAT score, response to DDAVP challenge and HMB therapy)	3 years

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: Shire
• Investigators: Principal Investigator: Sarah Sartain, MD, Texas Children's Hospital, an affiliate of Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2017
• Primary Completion (Actual): June 1, 2020
• Study Completion (Anticipated): November 1, 2025

Study Registration Dates

• First Submitted: October 10, 2016
• First Submitted That Met QC Criteria: October 12, 2016
• First Posted (Estimate): October 14, 2016

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Heavy Menstrual Bleeding; Bleeding Disorders
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Blood Platelet Disorders; Von Willebrand Diseases
• Other Study ID Numbers: H-39295 LOW VWF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No