Identifying the Determinants of Bleeding and Hypermobility in Patients With Heavy Menstrual Bleeding

Sponsor

St. Jude Children's Research Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05685199

Collaborator

Wallace H. Coulter Foundation (Other)

150

Enrollment

Location

84.9

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this study, researchers want to learn about the connection between heavy bleeding issues and joint hypermobility (loose joints). They want to know if these issues may indicate other connective tissue problems in girls and women with heavy menstrual bleeding who do not have a known cause.

Primary Objective

Compare the severity of heavy menstrual bleeding (HMB) in women with and without Generalized joint Hypermobility Syndrome Disorder/hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS).

Secondary Objectives

Compare the severity of heavy menstrual bleeding (HMB) in women with and without Generalized joint Hypermobility Syndrome Disorder/hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS).

Condition or Disease	Intervention/Treatment	Phase
Hypermobile Ehlers-Danlos Syndrome Heavy Menstrual Bleeding Hypermobility Syndrome (Disorder)

Detailed Description

The researchers will screen for patients referred to St. Jude due to heavy menstrual bleeding (HMB). Patients will be eligible for inclusion and offered to be screened for enrollment in this study if the duration of their menses was greater than or equal to 7 days, and they reported either "flooding" or bleeding through a tampon or napkin in 2 hours or less with most periods, and have no identifiable bleeding disorder. A Self-BAT score of ≥6 is required for eligibility for study enrollment.

Once enrolled, joint hypermobility will be evaluated using a Beighton score which will be used to assign participants to two groups: with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS). Participants will then undergo a detailed clinical examination to further classify them using the 2017 diagnostic criteria and complete symptom questionnaires. Finally, participants will be consented to TBANK (NCT01354002) and INSIGHT HD (NCT02720679) so as to provide a sample of leftover blood for banking for future research. Participants will be seen annually for the next 3 years as part of their standard of care to document the course of their symptoms.

Visit 1: Self-BAT Questionnaire, Beighton Score examination, 2017 hEDS examination, PROMIS (Peds/Parent) questionnaire, PHQ15 questionnaire, COMPASS31 questionnaire, Menstrual distress questionnaire (ENDOPAIN), and Heavy menstrual bleeding checklist (both pediatric and adult).

Visit 2: Self-BAT Questionnaire, PROMIS (Peds/Parent) questionnaire, PHQ15 questionnaire, COMPASS31 questionnaire, Menstrual distress questionnaire (ENDOPAIN).

Visit 3: Self-BAT Questionnaire, PROMIS (Peds/Parent) questionnaire, PHQ15 questionnaire, COMPASS31 questionnaire, Menstrual distress questionnaire (ENDOPAIN).

Study Design

Study Type:

Observational

Anticipated Enrollment :

150 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Identifying the Determinants of Bleeding and Hypermobility in Patients With Heavy Menstrual Bleeding

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

Mar 1, 2030

Arms and Interventions

Arm	Intervention/Treatment
Case Group Participants with heavy menstrual bleeding (HMB)
Control Group Participants without heavy menstrual bleeding (HMB)

Outcome Measures

Primary Outcome Measures

Severity of bleeding symptoms in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS). [Yearly for 3 years]
Summary statistics of bleed score including mean, median, standard deviation and range will be reported for women with and without G-HSD/hEDS.
Number of patients with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS). [Approximately 3 years]
The number of patients with G-HSD/hEDS will be reported
Proportion of patients with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS). [Approximately 3 years]
The proportion of patients with G-HSD/hEDS will be reported

Secondary Outcome Measures

Co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS) - PHQ15 [Yearly for 3 years]
We will compare co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS) using PHQ 15. The PHQ-15 is a subscale of the full Patient Health Questionnaire (PHQ) and screens for 15 somatic symptoms. It scores symptom presence and severity on a 3-point Likert scale (0-2). The total score ranges from 0-30 with higher values indicating increased severity as follows: Minimal (0-4); Low (5-9); Medium (10-14); High (15-30).
Co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS): Peds Patient-reported Outcomes Measurement Information System (PROMIS) 49 and Parent Proxy 49 [Yearly for 3 years]
We will compare co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS) using Peds PROMIS 49 and Parent Proxy 49. The Peds PROMIS 49 is self-reported measures of global, physical, mental, and social health for children (ages 8-17) in the general population and those living with a chronic condition. The Parent Proxy 49 is intended for parents serving as proxy for their child (youth ages 5-17). PROMIS scores are reported as T scores ranging from 0-100. A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like Anxiety, a T-score of 60 is one SD worse than average. By comparison, an Anxiety T-score of 40 is one SD better than average. However, for positively-worded concepts like Physical Function-Mobility, a T-score of 60 is one SD better than average while a T-score of 40 is one SD worse than average.
Co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS): PROMIS 57 [Yearly for 3 years]
We will compare co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS) using adult PROMIS 57. The PROMIS 57 is for self-reporting measures of global, physical, mental, and social health for adults in the general population and those living with a chronic condition. PROMIS scores are reported as T scores ranging from 0-100. A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like Anxiety, a T-score of 60 is one SD worse than average. By comparison, an Anxiety T-score of 40 is one SD better than average. However, for positively-worded concepts like Physical Function-Mobility, a T-score of 60 is one SD better than average while a T-score of 40 is one SD worse than average.
Co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS): Compass 31 [Yearly for 3 years]
We will compare co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS) using COMPASS31. The COMPASS31 contains 31 questions with Likert scales ranging in length from 2 to 6 items with higher scores indicating increased severity. COMPASS31 provides raw scores and standardized scores providing a total weighted score (0-100) of severity. The scale yields 6 subscales and a total score as follows: Orthostatic intolerance (4-10), Vasomotor (3-6); Secretomotor (4-7); Gastrointestinal (12-28); Bladder (3-9); Pupillomotor (5-15); Total (31-75)
Co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS): Menstrual Distress Questionnaire [Yearly for 3 years]
We will compare co-morbidities in women with and without Generalized joint Hypermobility Syndrome Disorder/ hypermobile Ehlers-Danlos Syndrome (G-HSD/hEDS)using the Menstrual Distress Questionnaire. This is a 21-element survey (ENDOPAIN 4D) which measures the gynecological and pelvic pain symptoms associated with periods. Each question is on a 11-point Likert scale with higher scores reflecting more severe symptoms or symptoms that most closely resemble the description.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 40 Years

Sexes Eligible for Study:

Female

Inclusion Criteria:

Female
12-40 years of age
Not currently pregnant
No documented uterine structural abnormality
Self-BAT score of ≥6
Prothrombin Time/ activated Partial Thromboplastin Time/Fibrinogen and Von Willebrand Factor activity, antigen and Factor 8 are not reflective of a bleeding disorder

Exclusion Criteria:

Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
Current use of anticoagulant and antiplatelet medications
Medical conditions that could cause heavy menstrual bleeding but are not necessarily a bleeding disorder including, but not limited to:
Uncontrolled hypertension,
Insulin Dependent Diabetes Mellitus,
Chronic Kidney Disease,
Chronic Liver Disease,
Thyroid disease,
Documented Peripheral Arterial Disease, venous or arterial vascular events in the past
A structural pathology that would explain the Heavy Menstrual Bleeding
Persistent thrombocytopenia as defined by a platelet count of <150,000/uL
If the participant answers "yes" to any of the pre-screening questions:
Could the patient have a known connective tissue disorder?
Family history of sudden death
Family history/personal history of uterine rupture or bowel perforation
Family history/personal history of arterial rupture
Family history/personal history of aneurysm
Family history/personal history of an established Ehlers Danlos Syndrome diagnosis based on genetic evaluation