Growth Hormone DeficiencyNCT02243852
Effects of Growth Hormone (GH) Deficiency and Growth Hormone Replacement on Serum Fibroblast Growth Factor 21 (FGF21)
An observational study of Growth Hormone Deficiency, run by University of Liverpool at 2 sites in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Growth Hormone Deficiency
- What is being tested?
- Growth Hormone Replacement Therapy
- How many people
- 0 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Sep 2014to 6 Jun 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Secondary care clinic University advertisement
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Withdrawal criteria: Patients will be withdrawn from the study if they discontinue their growth hormone replacement therapy for any clinical reason.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
MARIARC
Liverpool, Merseyside, L69 3GE
University Hospital Aintree
Liverpool, Merseyside, L9 7AL
About this study
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)
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.
Read the detailed 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.
- Conditions
- Growth Hormone Deficiency
- Being tested
- Growth Hormone Replacement Therapy
- Keywords
- Growth Hormone Deficiency (GHD), Growth Hormone Replacement Therapy, Fibroblast Growth Factor 21 (FGF21), Visceral Fat, Subcutaneous Fat
- Medical subject headings
- Dwarfism, Pituitary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Growth Hormone Replacement TherapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Growth Hormone Deficiency (n=16) | 16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement) will be compared with 16 healthy controls. Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be assessed in each of cohort to determine the correlation of FGF21 levels with VAT, SAT and liver fat. | |
| Healthy Controls (n=16) | 16 healthy controls will be compared with 16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement). Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be measured in all cohorts to determine the correlation of FGF21 levels with VAT, SAT and liver fat. | |
| Growth Hormone Replacement Therapy (n=16) | GHD patients, who are eligible for GH replacement therapy as part of their routine clinical care, according to the National Institute for Clinical Excellence (NICE) recommendations, based on the biochemical deficiency and the appropriate AGHDA questionnaire score (AGHDA score>11) will be recruited. These patients attend the Joint Endocrine clinic at University Hospital Aintree, Liverpool, and those who are about to commence growth hormone replacement will be asked to participate in this observational study.
Anthropometric, biochemical including measurement of FGF21 and MR evaluation will be carried out in patients who are to be treated with GH as part of their routine clinical care immediately prior to GH therapy and after six months of replacement treatment. The type of GH and dose of treatment will be at the discretion of the treating physician. Standard doses will be used and patients will remain under the care of the supervising Receives: Drug: Growth Hormone Replacement Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6-months
Secondary outcomes (1)
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.
Measured: 6-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionAug 2015 (estimated)
- Study completion6 Jun 2017
Why it stopped: Sponsor withdrew support 6th June 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Growth Hormone DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Daniel J Cuthbertson, PhD, Principal investigator, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02243852
- Sponsor's protocol ID
- 13/NW/0075
- Status last verified
- Sep 2014
- First submitted
- 16 Sep 2014
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02243852
- Acronym / sponsor ID
- 13/NW/0075
- Conditions
- Growth Hormone Deficiency
- Keywords
- Growth Hormone Deficiency (GHD), Growth Hormone Replacement Therapy, Fibroblast Growth Factor 21 (FGF21), Visceral Fat, Subcutaneous Fat
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Sponsor withdrew support 6th June 2017
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Sep 2014
- Primary completion
- Aug 2015 (estimated)
- Study completion
- 6 Jun 2017 (actual)
- First posted
- 18 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Growth Hormone Deficiency (n=16) | – | –16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement) will be compared with 16 healthy controls. Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be assessed in each of cohort to determine the correlation of FGF21 levels with VAT, SAT and liver fat. |
| Healthy Controls (n=16) | – | –16 healthy controls will be compared with 16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement). Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be measured in all cohorts to determine the correlation of FGF21 levels with VAT, SAT and liver fat. |
| Growth Hormone Replacement Therapy (n=16) | – | Drug: Growth Hormone Replacement TherapyGHD patients, who are eligible for GH replacement therapy as part of their routine clinical care, according to the National Institute for Clinical Excellence (NICE) recommendations, based on the biochemical deficiency and the appropriate AGHDA questionnaire score (AGHDA score>11) will be recruited. These patients attend the Joint Endocrine clinic at University Hospital Aintree, Liverpool, and those who are about to commence growth hormone replacement will be asked to participate in this observational study. Anthropometric, biochemical including measurement of FGF21 and MR evaluation will be carried out in patients who are to be treated with GH as part of their routine clinical care immediately prior to GH therapy and after six months of replacement treatment. The type of GH and dose of treatment will be at the discretion of the treating physician. Standard doses will be used and patients will remain under the care of the supervising |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Secondary care clinic University advertisement
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Growth Hormone Replacement TherapyAn 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. | Drug | Growth Hormone Replacement Therapy (n=16) |
Primary outcome
FGF21
Time frame: 6-months
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
1 secondary outcome
Visceral and subcutaneous fat
Time frame: 6-months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
Related trials for Growth Hormone Deficiency
RecruitingPhase 3
Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders
Turner Syndrome, Short Stature Homeobox Gene Mutation
RecruitingPhase 3
Randomized Clinical Trial of Two Different Initial Growth Hormone Doses in Children
Growth Disorders, Growth Failure
RecruitingPhase 3
Phase 3 Study of LUM-201 in Children With Growth Hormone Deficiency
Growth Hormone Deficiency (GHD)
RecruitingPhase 3
Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)
Adult Growth Hormone Deficiency, Mild Traumatic Brain Injury
Enrolling by invitationObservational study
Influence of Adherence to Growth Hormone Therapy (GHT) With Norditropin® on Near Final Height in Patients With Growth Hormone Deficiency (GHD) and Born Small for Gestational Age (SGA)
Growth Hormone Deficiency in Children, Born Small for Gestational Age
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel J Cuthbertson, PhD principal investigator
University of Liverpool
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Growth Hormone Deficiency, run by University of Liverpool at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FGF21 (time frame: 6-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.