The use of recombinant growth hormone to improve growth and health in children and young adults with cystic fibrosis

Review question

We reviewed the evidence about the effects of man-made human growth hormone on growth and health of people with cystic fibrosis.

Background

Cystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive system (gut) and pancreas. People with cystic fibrosis are often underweight and have delayed growth. Nutritional supplements may not be enough to improve growth and it has been suggested that treatment with man-made human growth hormone might help. Human growth hormone is usually given once a day via a needle under the skin. It can improve the rate of growth and bone density in children and young adults, but may also affect glucose metabolism which has implications for children at risk of cystic fibrosis-related diabetes. Treatment is also expensive, so a review needs to look at the risks and benefits of this treatment.

Search date

The evidence is current to: 11 February 2015.

Study characteristics

This review looked at the use of man-made human growth hormone to improve lung function, growth and quality of life for children and young adults with cystic fibrosis. It includes four trials with 161 volunteers who were selected for one treatment or the other randomly. The volunteers were 7 - 23 years old, but most of them had not reached puberty. Three trials lasted for one year and one for six months. Hormone treatment was compared to no treatment in three trials and to placebo (liquid that didn't contain any growth hormone) in one trial. The trial that used a placebo compared this to two different dose levels of hormone treatment.

Key results

The trial results showed a modest improvement in height and weight over 6 to 12 months. However, we did not find any consistent evidence in the improvement of lung function, muscle strength, clinical condition or quality of life after treatment. We also did not find any effects on glucose metabolism or the long-term risk of diabetes due to the treatment. Given these results, we are not able to identify any clear benefit of therapy and believe that more research from well-designed, large trials is needed.

Quality of the evidence

We did not have enough information to decide if overall the trials were biased in such a way to affect the results. We were happy that all the outcomes that were measured were clearly reported in the trials, but there were some concerns that outcomes based on personal judgement, like quality of life scores, might be affected because the volunteers in the three trials comparing treatment to no treatment would know which group they were in.

Authors' conclusions: 

Recombinant growth hormone therapy is effective in improving the intermediate outcomes in height, weight and lean tissue mass when compared with no treatment. One measure of pulmonary function test showed moderate improvement at a single time point, but no consistent benefit was seen across all studies. No significant changes in quality of life, clinical status or side-effects were observed in this review. Long-term, well-designed randomised controlled trials of recombinant growth hormone therapy in people with cystic fibrosis are required prior to evaluation of human growth hormone treatment for routine use.

Read the full abstract...
Background: 

Cystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with cystic fibrosis often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant growth hormone, has been proposed as a potential intervention.

Objectives: 

To evaluate the effectiveness and safety of recombinant human growth hormone therapy in improving lung function, quality of life and clinical status of children and young adults with cystic fibrosis.

Search strategy: 

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 11 February 2015.

We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Scopus and Proceedings First. Date of latest search: 04 March 2015.

Selection criteria: 

Randomised and quasi-randomised controlled trials of all preparations of recombinant growth hormone compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults aged up to 25 years diagnosed with cystic fibrosis (by sweat test or genetic testing).

Data collection and analysis: 

Two authors independently screened papers, extracted trial details and assessed their risk of bias.

Main results: 

Four controlled trials were included in this review (with 161 participants in total), each with an unclear risk of bias. Analysis of data obtained from these trials shows improvement in height for all comparisons, but improvements in weight and lean tissue mass were only reported in the comparison of standard dose recombinant growth hormone versus no treatment. One study showed moderate improvement at one time point in one parameter of pulmonary function tests, forced vital capacity (per cent predicted) when comparing standard dose recombinant growth hormone and no treatment, but there was no consistent benefit in lung function across all studies. Little evidence was found for improvement in quality of life. An improvement in fasting blood glucose levels was reported when comparing rhGH to placebo only. Exercise capacity improved in participants receiving standard dose recombinant growth hormone versus no treatment, but not for any other comparison. There is insufficient evidence to conclude any changes in hospitalisations, antibiotic use or significant adverse effects.

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