The effects of pubertal induction on bone health in children with neuromuscular conditions

Status

Recruiting

Phases

Phase 3

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12619001372178

Acronym

PIMS

Enrollment

Registered

2019-10-08

Start date

2018-09-18

Completion date

Unknown

Last updated

2019-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

This study is a prospective, interventional study of bone health in children with neuromuscular diseases conducted at The Royal Children’s Hospital, Melbourne. The effect(s) of pubertal induction in paediatric neuromuscular diseases have not been formally studied. Our main aim is to provide evidence as to whether pubertal induction may improve bone health and quality of life in children and adolescents with significant neuromuscular disabilities and reduce burden of care on families. Children with neuromuscular disabilities are often very thin and have poor muscle strength and stability, which increases fall frequency and risk of fracture and often have delayed or arrested puberty. Puberty is a crucial time for bone mass accrual and therefore, an optimal time for clinicians to intervene to improve bone health.

Interventions

BOYS: transdermal testosterone (Testogel) rubbed into the thigh daily (either dispensed via sachet or pump depending on product availability) GIRLS: transdermal oestrogen patch (Climara) placed on hairless skin area weekly (continuously for 7 days) Please see algorithm for dose changes below: All dosing changes are based on the participant’s preceding visit. BOYS: Screening – 3 months: All participants will start at ½ Sachet or 2 actuations of pump daily At 3 months visit: If there is an increase of AT LEAST one level of Tanner staging = No changes If there is no changes to puberty = Increase to 1 sachet /day (for sachets) or 4 actuations daily (for pump) At 6 months visit: If there is an increase of AT LEAST one level of Tanner staging = No changes If there is no changes to puberty and patient is only on starting dose= Increase to 1 sachet/4 actuations daily If there is no changes to puberty and patient is currently on 1 sachet/4 actuations, increase to 2 sachets daily/8 actuations daily At 9 months visit: If there is an increase of AT LEAST one level of Tanner staging = No changes If there is no changes to puberty and patient is only on starting dose= Increase to 1 sachet/4 actuations daily If there is no changes to puberty and patient is currently on 1 sachet/4 actuations, increase to 2 sachets daily/8 actuations daily If there is no changes to puberty and patient is currently on 2 sachets daily/8 actuations daily, make no further changes as this is the maximum dose. At 12 months visit: If there is an increase of AT LEAST one level of Tanner staging = No changes If there is no changes to puberty and patient is only on starting dose= Increase to 1 sachet/4 actuations daily If there is no changes to puberty and patient is currently on 1 sachet/4 actuations, increase to 2 sachets daily/8 actuations daily If there is no changes to puberty and patient is currently on 2 sachets daily/8 actuations daily, make no further changes as this is the maximum dose. From 12- 24 months visit: No further changes to dosage - maintain current dose GIRLS: Screening – 3 months: All participants will start at ½ patch of Climara® 25, weekly At 3 months visit: If patient has an increase of AT LEAST one level of Breast Tanner staging = No changes If patient has no changes to puberty = Increase to one patch of Climara® 25 weekly At 6 months visit: If patient has an increase of AT LEAST one level of Breast Tanner staging = No changes If patient has no changes to puberty and is on the starting dose= Increase to one patch of Climara® 25 weekly If patient has no changes to puberty and is currently on 1 full patch of Climara® 25 weekly = increase to 1 and a half patches of Climara® 25 weekly At 9 months visit: If patient has an increase of AT LEAST one level of Breast Tanner staging = No changes If patient has no changes to puberty and is on the starting dose= Increase to one patch of Climara® 25 weekly If patient has no changes to puberty and is currently on 1 full patch of Climara® 25 weekly = increase to 1 and a half patches of Climara® 25 weekly If patient has no changes to puberty and is currently on 1 and half patches of Climara® 25 weekly = increase to one patch of Climara® 50 weekly At 12 months visit: If patient has an increase of AT LEAST one level of Breast Tanner staging = No changes If patient has no changes to puberty and is on the starting dose= Increase to one patch of Climara® 25 weekly If patient has no changes to puberty and is currently on 1 full patch of Climara® 25 weekly = increase to 1 and a half patches of Climara® 25 weekly If patient has no changes to puberty and is currently on 1 and half patches of Climara® 25 weekly = increase to one patch of Climara® 50 weekly If patient has no changes to puberty and is currently on 1 full patch of Climara® 50 weekly = no changes as this is the maximum dose From 12- 24 months visit: No further changes to dosage - maintain current dose Medication refills will occur 3-monthly. Compliance will be monitored by counting scripts not filled (from missed visits) and unused patches, as well as self-reports by patient using medication log/diary. For those who decline treatment, these children will undergo the assessments at baseline, 12 and 24 months as outlined previously without the 3 monthly check-ups.

Study design

Allocation

Non-randomised trial

Primary purpose

Treatment

Eligibility

Sex/Gender

All

Age

13 Years to 18 Years

Healthy volunteers

Inclusion criteria

Participants will include girls 13 years and over, and boys 14.5 years and older, who have not reached puberty as defined by onset of breast development in girls, testicular enlargement in boys >4ml , with associated and continuing changes in feminization or virilisation over at least 6 months and who have one of the following conditions 1) Spinal muscular atrophy Types 2 & 3 2) Cerebral palsy with a level 4 or 5 on the Gross Motor Function Classification System (GMFCS) 3) Muscular dystrophies other than Duchenne (eg Becker) and congenital myopathies (eg. Nemaline )

Exclusion criteria

Children who • Have Duchenne Muscular Dystrophy (because of corticosteroid use interferes with pubertal onset and progress) • Are currently participating in other trials because altered pubertal status is likely to affect other care aspects in many areas • Are using or have prior use of bisphosphonates or other bone modifying drugs • Have used corticosteroids for the last 12 months • Has active or completed puberty • Have a contraindication to Androgens (Testogel®) or oestrogens (Climara®) use due to a severe pro-coagulopathic disorder or medication allergies • Have vertebral fractures greater than Genant 3 found on back x-ray at screening or 6 months prior as this will require bisphosphonate treatment • Previous incidences of deep vein thrombosis, clots or stroke • Older than 18 years of age

Outcome results