Skeletal Health and Bone Marrow Composition Among Youth

NCT04203381 | Active Not Recruiting DMC

• 1 other identifier: P00033841
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Children and adolescents experiencing gender dysphoria feel increased distress with the onset of puberty. Gender clinics treat these young adolescents by "blocking" puberty using gonadotropin-releasing hormone (GnRH) agonist medications. This has the possibility of impacting bone development as sex steroids are important to bone mass development. In this multi-site study, the investigators will examine bone marrow composition (by MRI) in 40 transgender youth and bone density and body composition before/after pubertal blockade compared to healthy participants.

Conditions

Gender Dysphoria in Children; Puberty; Bone Development

Outcome Measures

Primary Outcomes (2)

• Change from Bone marrow adiposity by magnetic resonance imaging (MRI) from baseline compared to 24 months

  Change from bone marrow adiposity measured by MRI (T1 maps) from baseline compared to 24 months

  Change from baseline compared to 24 months

• Change from magnetic resonance spectroscopy (MRS) from baseline compared to 24 months

  Change from T2 corrected fat/(fat+ water) ratios from baseline compared to 24 months

  Change from baseline compared to 24 months

Secondary Outcomes (5)

• Change from total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA) from baseline compared to 24 months

  Change from baseline compared to 24 months

• Change from spine BMD Z-score by DXA from baseline compared to 24 months

  Change from baseline compared to 24 months

• Change from hip BMD Z-score by DXA from baseline compared to 24 months

  Change from baseline compared to 24 months

• Change from volumetric bone mineral density (vBMD) from baseline compared to 24 months

  Change from baseline compared to 24 months

• Change from section modulus (bone bending strength) by quantitative computed tomography (pQCT) from baseline compared to 24 months

  Change from baseline compared to 24 months

Other Outcomes (3)

• Change from health-related quality of life (HRQL) from baseline compared to 24 months

  Change from baseline compared to 24 months

• Change from anxiety from baseline compared to 24 months

  Change from baseline compared to 24 months

• Change from depression from baseline compared to 24 months

  Change from baseline compared to 24 months

Study Arms (2)

Transgender Participant

OTHER

Transgender children at Tanner stage II or early Tanner stage III between the ages of 9 and 14. Must be a current patient at a gender patient and within 6 weeks of initiating pubertal blockade treatment

Device: GnRH Agonist

Cisgender Control Participant

NO INTERVENTION

Cisgender children Tanner II or early Tanner III between 9 and 14 matched by race, age, and BMI.

Interventions

GnRH Agonist DEVICE

Forty participants who are transgender and who have been prescribed a gonadotropin-releasing hormone (GnRH) agonist by their physician will undergo magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans at baseline, at 12 months and at 24 months after initiation of the GnRH agonist therapy. This longitudinal observational study of two cohorts seeks to identify significant changes in bone marrow adiposity and bone density over 24 months. The same assessments will be obtained in 40 healthy control subjects matched for age, race/ethnicity and body mass index, all factors that are known to influence skeletal outcomes. The evaluations of bone marrow adiposity will be correlated with bone density measurements and the assessments of mood (validated anxiety and depression scales) and health-related quality of life, before and after pubertal blockade.

Also known as: Histrelin, Lupron, Pubertal Blockade

Transgender Participant

Eligibility Criteria

• Age: 9 Years - 14 Years
• Gender Eligibility Details: Participants must identify as transgender or nonbinary to be eligible for the study.
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Be willing to give informed consent/assent (parent or legal guardian able to provide informed consent)
• Tanner Stage II/III
• Age 9-14 years old for assigned male at birth (AMAB) and 9-13 for assigned female at birth (AFAB)
• Current patient at the Boston Children's Hospital Transgender Clinic or Cincinnati Children's Hospital Medical Center Clinic, within six weeks of initiating pubertal blockade treatment (e.g., GnRH agonist- Lupron or Vantas)
• Controls are matched on age within 2 years, race/ethnicity, sex assigned at birth and BMI within 25%

You may not qualify if:

• The participant must not:
• Have chronic disease known to affect skeletal metabolism (e.g. cystic fibrosis, celiac disease, sickle cell disease, inflammatory bowel disease etc.)
• Receipt of other medications within previous 3 months known to affect skeletal metabolism (e.g., glucocorticoids, anticonvulsants, etc.)
• Have metal implants or hardware in their body that would not allow them to get an MRI
• Have a diagnosis of a developmental disorder or claustrophobia that would prevent them from undergoing an MRI

Sponsors & Collaborators

• Amy DiVasta, MD: lead
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (2)

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Adolescent Medicine

Study Record Dates

• First Submitted: December 11, 2019
• First Posted: December 18, 2019
• Study Start: September 15, 2020
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)