Testosterone Therapy for Pubertal Delay in Duchenne Muscular Dystrophy

Observational Study of Clinical Outcomes for Testosterone Treatment of Pubertal Delay in Duchenne Muscular Dystrophy

"Observational study of clinical outcomes for testosterone treatment of pubertal delay in Duchenne Muscular Dystrophy" is a single centre observational study that aims to follow the progress of 20 adolescents with Duchenne Muscular Dystrophy (DMD) and delayed puberty who are treated by the Newcastle muscle team, as they are treated with testosterone to induce puberty. The participants will all be treated with the standard stepwise regimen of testosterone injections every 4 weeks and data will be collected to help determine the effectiveness and tolerability of the current treatment regimen. The investigators will use the data to explore the effect of testosterone on pubertal development, growth, muscle strength and function, bone mineral density and body composition and characterise any side effects. Semi-structured interviews will also be carried out to learn the boys' views on the tolerability of the regimen. The study will last up to a maximum of 27 months in total for each participant, but may be less if they are happy with pubertal development before this time. It is important to do this study because from the investigator's limited experience in this group, testosterone treatment seems to be well liked and tolerated but the best treatment regimen to use remains unknown and there is no current consensus. It is not currently part of the standard of care in DMD but it would be important to include it if this study can show that it is an effective treatment for pubertal delay.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Sustanon (testosterone)

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• United Kingdom
  • Newcastle Upon Tyne, United Kingdom, NE1 3BZ
    • Institute of Genetic Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

This is a single-centre, prospective, observational, study on clinical outcomes of testosterone replacement therapy in adolescents with DMD and delayed puberty. Being an observational study of routine care, there will be no specified end point. We will aim to recruit any adolescent with DMD and delayed puberty who is reviewed by the muscle team at the John Walton Muscular Dystrophy Research Centre from the study approval date.

Description

Inclusion Criteria:

• A molecular diagnosis of Duchenne Muscular Dystrophy.
• Males aged between 12 and 17 years of age at time of first dosing
• Prepubertal (Tanner stage 1, testicular volume <4 mls, initial testosterone level of <2.0 nmol/l)
• Subjects are receiving the standard of care for DMD as recommended by the NorthStar UK and TREAT-NMD guidelines
• Patients are capable of sitting upright in a wheelchair for at least an hour
• Patients have stable respiratory function. Artificial ventilation with either Bipap/continuous positive airways pressure (CPAP) or tracheostomy is not a contraindication to the study.
• Informed consent/assent signed by the patient (or parent/guardian if under 16 years of age)

Exclusion Criteria:

• Severe learning difficulties that would preclude them from cooperating with examination.
• Anticipated surgery during the study period.
• Symptomatic cardiac failure.
• Participants/families who may have emotional or psychological problems if recruited to a study
• Hypersensitivity to the active substance or to any of the excipients, including arachis oil or derivatives (including hypersensitivity and allergy to peanuts or soya.)
• Any contra-indication to receiving an intramuscular injection
• Any additional chronic disease that affects androgen production
• Anti-coagulant therapy
• If participation in the study is not recommended in the opinion of the investigators

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total score in the Treatment Satisfaction Questionnaire for Medication (TSQM)	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Subject's reported effectiveness of testosterone therapy as assessed by semi-structured interviews pre and post treatment	2 years
Total score in Northstar Ambulatory Assessment or Performance of the Upper Limb if non-ambulant	2 years
Z-score from Bone mineral adjusted density of the lumbar spine and total body (minus head) using Dual Xray Absorptiometry (DXA)	2 years
Percentage of body mass assessed by DXA	2 years
Osteocalcin level, measured by blood test	2 years
P1NP level, measured by blood test	2 years
Percentage fat fraction as assessed by muscle Magnetic Resonance Imaging (MRI) of upper and lower limbs	2 years
Pubertal staging assessed using Tanner staging and testicular volume	2 years
Bone age as assessed by wrist and hand X-Ray	2 years
Hormonal assessment of pubertal staging using testosterone level	2 years
Forced vital capacity, measured by spirometry	2 years
Cardiac function, assessed by Electrocardiogram (ECG) and echo	2 years

Collaborators and Investigators

• Sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
• Investigators: Principal Investigator: Michela Guglieri, Newcastle University

Publications and helpful links

General Publications

• Wood CL, Cheetham TD, Hollingsworth KG, Guglieri M, Ailins-Sahun Y, Punniyakodi S, Mayhew A, Straub V. Observational study of clinical outcomes for testosterone treatment of pubertal delay in Duchenne muscular dystrophy. BMC Pediatr. 2019 Apr 25;19(1):131. doi: 10.1186/s12887-019-1503-x.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): February 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: August 24, 2015
• First Submitted That Met QC Criteria: October 7, 2015
• First Posted (Estimate): October 8, 2015

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 12, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: testosterone; pubertal delay
• Additional Relevant MeSH Terms: Nervous System Diseases; Endocrine System Diseases; Gonadal Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Puberty, Delayed; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: 2015-003195-68

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data available on request