Effects of Growth Hormone (GH) Deficiency and Growth Hormone Replacement on Serum Fibroblast Growth Factor 21 (FGF21)

Growth Hormone Deficiency Clinical Trial

Official title:

Evaluation of the Effects of Growth Hormone (GH) Deficiency and Growth Hormone Replacement on Serum Fibroblast Growth Factor 21 (FGF21) Concentration in Patients With Growth Hormone Deficiency (GHD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02243852
• Other study ID #: 13/NW/0075
• Status: Recruiting
• Phase: N/A
• First received: September 16, 2014
• Last updated: September 18, 2014
• Start date: September 2014

Study information

• Verified date: September 2014
• Source: University of Liverpool
• Contact: Daniel J Cuthbertson, PhD
• Phone: +441515295911
• Email: daniel.cuthbertson[@]liverpool.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial Summary

This study will recruit healthy controls (who have normal GH production and growth hormone levels) and patients identified as having GHD, who are deemed eligible for GH replacement therapy according to NICE guidelines. The patients recruited will have been identified as starting on GH by their referring clinicians and a decision made on their replacement therapy prior to their potential enrollment in the study. The study, or its research team, will have no influence on the decision as to whether a patient will start on GH, or on which of the many GH formulations that the patients receives. The proposed study is an observational study to determine how GH affects the plasma levels of Fibroblast growth factor 21 (FGF21) in response to treatment; and whether the change in FGF21 mirrors the improvement in body composition/fat deposition. FGF21 is a metabolic regulator that acts on multiple tissues to coordinate carbohydrate and lipid metabolism and regulate energy balance.

We hypothesize that FGF-21 is expressed and secreted from liver and skeletal muscle in humans in response to growth hormone administration and that levels may be reduced in patients with GHD compared with healthy controls. Furthermore, we believe that the beneficial effects of long-term GH replacement on body composition (reduction in visceral adipose tissue, subcutaneous adipose tissue and liver fat), on improvement in lipid profiles and on skeletal muscle mitochondrial function involve GH-induced release of FGF21.

Description:

Growth hormone (GH) is involved in controlling people's general health and an underproduction of growth hormone (growth hormone deficiency or GHD) leads to people feeling generally unwell and having a lower feeling of well-being and quality of life scores. In addition, the investigators, and others, have demonstrated people with GHD have reduced muscle and bone strength and a greater storage of fat, particularly in unfavourable sites such as in the liver and within the abdomen (visceral fat), rather than beneath the skin (subcutaneous fat).

Treatment of GHD is achieved by administration of GH replacement therapy, given as a once daily subcutaneous injection, which generally reverses these symptoms. Due to its high cost, patients are only started on GH replacement depending on the impact that the GHD is having on their quality of life. Patients must be severely affected to be eligible for replacement therapy. Patients are screened for quality of life using a well validated, disease specific questionnaire (AGHDA, Adult Growth hormone deficiency questionnaire) and there are specific criteria that govern whether a patient with GHD warrants GH replacement and also whether they continue treatment (NICE guideline: Growth hormone deficiency (adults) - human growth hormone (TA64)).

This study will specifically determine whether the mechanism of action by which GH exerts its beneficial effects on metabolism (within adipose tissue and skeletal muscle) involves changes in serum FGF21 concentrations.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

All evaluations to determine eligibility into the study and for growth hormone replacement are performed as part of routine clinical care. It should be emphasised that no research specific screening tests will be performed. Patients deemed eligible for entry into study, who decline to participate in the research, will still be commenced on growth hormone in line routine clinical care.

Inclusion criteria: Patients with confirmed GH deficiency who are deemed eligible for GH replacement as assessed by the AGHDA QOL questionnaire.

Exclusion criteria: Claustrophobia or having significant metal work is a contra-indication to MRI scanning.

Withdrawal criteria: Patients will be withdrawn from the study if they discontinue their growth hormone replacement therapy for any clinical reason.

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency

Intervention

Drug:
• Growth Hormone Replacement Therapy
An observational study of patients who are commencing GH replacement as part of their routine NHS clinical care to assess changes in serum FGF21 concentration and determine how these relate to changes in body composition.

Locations

Country	Name	City	State
United Kingdom	MARIARC	Liverpool	Merseyside
United Kingdom	University Hospital Aintree	Liverpool	Merseyside

Sponsors (2)

Lead Sponsor	Collaborator
University of Liverpool	Pfizer

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FGF21	The primary outcome measure involves differences in serum FGF21 concentration between healthy controls and GHD patients, and changes in FGF21 concentration with GH replacement in patients with GHD	6-months	No
Secondary	Visceral and subcutaneous fat	Differences in visceral and subcutaneous fat volume between healthy controls and GHD patients.; Changes in visceral and subcutaneous fat volume after 6 months of GH.	6-months	No