Pubertal Blockade and Hormone Therapy in Transgender Youth (PUBErTY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03557268
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : July 19, 2018
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
This study will enroll female-to-male transgender youth who are and are not on a puberty blocker (gonadotropin-releasing hormone analogue) at baseline and 1 and 12 months after starting testosterone. The study will evaluate markers of cardiometabolic health including: insulin sensitivity, laboratory markers, vascular health, body composition, activity/fitness, mitochondrial function and the microbiome.

Condition or disease
Gender Identity Gender Dysphoria Gender Identity Disorder in Adolescence and Adulthood

Detailed Description:

There will be a total of 6 study visits: baseline A, baseline B, 1 month after starting testosterone (visit A and B) and 12 months after starting testosterone (visit A and B). No medications will be administered as a part of this study.

Visit A procedures: Physical Examination, Laboratory, and Oral Glucose Tolerance Test (OGTT) visit.

This will be conducted at Childrens Hospital Colorado (CHCO) Clinical & Translational Research Centers (CTRC) facilities. Physical examination will include vital signs, anthropometric measurements, and breast/pubic hair staging as applicable (some subjects may have already undergone mastectomy/chest masculinizing surgery) by the PI. Subjects will fast for 8 hours prior to blood draw. Fasting blood work will be obtained, followed by an oral glucose load (75g glucola). Blood glucose and insulin concentrations will be drawn at baseline and 30, 60, 90 and 120 minutes after glucola administration. Serum will be obtained at baseline and 2 hours post-OGTT and used for bile acid and lipid metabolomic profile. The following questionnaires will be administered: REDCap Health Questionnaire, PedsQLTM 4.0 generic core questionnaire, PROMIS Pediatric Anxiety Short Form, PROMIS Pediatric Depressive Symptoms Short Form, Insomnia Severity Index, Morningness and Eveningness Scale. Participants will be mailed or emailed the 3-day dietary log prior to the visit and return it at this visit. They will be given a stool microbiome collection kit and urine collection kit to return at visit B. The medical chart will be reviewed for relevant health information and medications.

Part B: Vascular Imaging, MR-based imaging and spectroscopy, Exercise Capacity and Dual-energy X-ray (DXA) visit.

This will be conducted at the University of Colorado Denver Energy Balance Core and UCD Brain Imaging Center. The participant will be fasting for a minimum of 4 hours prior to the beginning of the study visit. The investigators will perform the tests in the following order:

  1. Participants will return stool microbiome and urine collection kit.
  2. Vascular imaging: carotid artery stiffness and intimal medial thickness and brachial artery flow-mediated dilation
  3. Magnetic Resonance (MR) based imaging and spectroscopy
  4. Oxygen consumption (VO2) peak exercise test on a stationary bicycle.
  5. Total body dual energy x-ray absorptiometry (DXA)
  6. Participants will be provided with an accelerometer and actigraphy watch to wear for a period of 7 days to measure level of habitual physical activity and sleep, respectively. They will also be provided a handout with instructions and a sleep and activity diary to be filled out each day during the 7 days of wear.

Study Type : Observational
Estimated Enrollment : 16 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effects of Pubertal Blockade and Hormone Therapy on Cardiometabolic Risk Markers in Transgender Adolescents
Actual Study Start Date : June 19, 2018
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : May 31, 2020

Resource links provided by the National Library of Medicine

On a GnRHa
Half of subjects will be on a puberty blocker or gonadotropin-releasing hormone analogue
Not on GnRHa
Half of subjects will NOT be on a puberty blocker or gonadotropin-releasing hormone analogue

Primary Outcome Measures :
  1. Change in Insulin sensitivity [ Time Frame: Baseline and 12 months after initiation of testosterone. ]
    Assessed by the Matsuda index, calculated from a 2-hour oral glucose tolerance test

  2. Change in Vascular Health [ Time Frame: Baseline and 12 months after initiation of testosterone. ]
    Brachial artery flow-mediated dilation

Secondary Outcome Measures :
  1. Change in Mitochondrial function [ Time Frame: Baseline and 12 months after initiation of testosterone. ]
    Hepatic mitochondrial function as assessed by 31Phosphorus- Magnetic Resonance Spectroscopy

  2. Change in VO2 peak [ Time Frame: Baseline and 12 months after initiation of testosterone. ]
    VO2 peak as measured on a bicycle ergometer

  3. Change in Body composition [ Time Frame: Baseline and 12 months after initiation of testosterone. ]
    as measured on a Dual-energy X-ray Absorptiometry (DXA) scan

Biospecimen Retention:   Samples Without DNA
Participants will have the options of banking plasma, serum, urine and stool for future research

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years to 16 Years   (Child)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female-to-male transgender youth
Sampling Method:   Non-Probability Sample
Study Population
16 female-to-male youth will be enrolled from 2 groups: 1) 8 female-to-male youth who have been on a gonadotropin-releasing hormone analogue for > 6 months; 2) 8 female-to-male (age-matched) youth who never received gonadotropin-releasing hormone analogue therapy.

Inclusion Criteria:

  • Identify as female-to-male
  • Age 13-16 years at the time of enrollment
  • If on a gonadotropin-releasing hormone analogue, > 6 months exposure
  • Plan to start testosterone clinically in < 6 months.

Exclusion Criteria:

  • Cognitive, psychiatric, or physical impairment resulting in inability to tolerate the study procedures
  • Diabetes
  • Antipsychotic medication
  • Hypertension (resting BP ≥ 140/90 mm/Hg)
  • Weight > 400 lbs (DXA and MRI limit)
  • On estrogen and/or progesterone medications

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 identifier (NCT number): NCT03557268

Contact: Natalie J Nokoff, MD 720-777-3607
Contact: Susan Staggs, BS 720-777-6128

United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Natalie Nokoff, MD    720-777-3607   
Sponsors and Collaborators
University of Colorado, Denver
Principal Investigator: Natalie J Nokoff, MD University of Colorado, Denver

Responsible Party: University of Colorado, Denver Identifier: NCT03557268     History of Changes
Other Study ID Numbers: 17-2328
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: July 19, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Gender Dysphoria
Sexual Dysfunctions, Psychological
Mental Disorders
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs