Muscle WeaknessNCT01847716
Transforming Growth Factor Beta Signalling in the Development of Muscle Weakness in Pulmonary Arterial Hypertension
An observational study of Muscle Weakness and Pulmonary Arterial Hypertension, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Pulmonary arterial hypertension (PAH) is a disease that causes raised blood pressure in blood vessels that pick up oxygen from the lungs. It has a life expectancy similar to some cancers. There is treatment available but there is no cure. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Muscle Weakness, Pulmonary Arterial Hypertension
- How many people
- 33 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2013to Aug 2016
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Clinics at Royal Brompton and Hammersmith hospital
Who may be able to join
- Patients with pulmonary arterial hypertension with New York Heart Association stage II - III disease will be eligible for recruitment in the patient portion of the trial. Interested healthy age matched volunteers will also be recruited.
Who cannot join
- Patients and volunteers will be excluded if they have significant co-morbidities including other cardiorespiratory disease, metabolic abnormalities including diabetes or thyroid disorders. They will be excluded if they cannot safely exercise and perform a six minute walk test or if they are wheelchair bound.
Trial locations and contacts
1 site in 1 country.
About this study
Pulmonary arterial hypertension (PAH) is a disease that causes raised blood pressure in blood vessels that pick up oxygen from the lungs. It has a life expectancy similar to some cancers. There is treatment available but there is no cure. We now know that PAH is associated with weakness in the muscles in the legs, which contributes to the symptoms patients' experience. Researchers believe that certain proteins found in high levels in the blood of patients with other chronic diseases can affect muscle function and growth. One of these proteins is called growth differentiating factor (GDF) 8, high levels of which are associated with muscle weakness in chronic obstructive pulmonary disease(COPD) and heart failure (HF). Interestingly there are drugs available which block the actions of GDF-8 on muscle cells which has been shown in animals to result in increased muscle size. A related protein called GDF-15 is found in elevated levels in patients PAH, and is linked to prognosis. Our preliminary data suggests that GDF-15 can also directly influence muscle size in a number of situations. We aim to investigate the role of GDF-15 and related molecules in the development of muscle weakness in patients with PAH. We will do this by measuring certain markers of muscle weakness and taking blood and muscle samples in patients and controls. We will then compare the levels of GDF-15 in these tissues in those with and without muscle wasting. We hope this work will lead to a greater understanding of the role of GDF-15 in the development of muscle weakness in patients with PAH. GDF-15 levels may be important in allowing us to define which patients have muscle weakness. In the future we aim to perform a clinical trial of drugs which block the actions of GDF-15.
- Conditions
- Muscle Weakness, Pulmonary Arterial Hypertension
- Keywords
- Muscle weakness, Pulmonary arterial hypertension, Transforming growth factor beta, Growth and differentiation factor 15
- Medical subject headings
- Muscle Weakness, Pulmonary Arterial Hypertension, Camurati-Engelmann Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| PH with wasting | This group of patients with idiopathic pulmonary arterial hypertension exhibit quadriceps wasting | |
| PH no wasting | This groups of patients with idiopathic pulmonary arterial hypertension exhibit no evidence of muscle wasting | |
| Controls | This group of volunteers does not have pulmonary arterial hypertension and would not be expected to have muscle wasting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma growth and differentiation factor 15 levels in participants with and without muscle wasting
Muscle wasting will be defined by quadriceps cross sectional area measured by ultrasound
Measured: 30 months
Secondary outcomes (12)
Correlation of plasma Growth and differentiation factor 15 levels with muscle strength
Muscle strength will be measured by quadriceps maximal volitional capacity percent predicted
Measured: 30 months
Change in fibre type in muscle biopsy
Measured: 30 months
GDF-15 levels in biopsy specimens
Measured: 30 months
Correlation of plasma Growth and differentiation factor 15 levels with brain natriuretic protein levels
Measured: 30 months
Correlation of plasma Growth and differentiation factor 15 levels with fat free mass index
Fat free mass index will be measured by bioelectrical impedence
Measured: 30 months
Correlation of plasma Growth and differentiation factor 15 levels with quality of life
Quality of life will be measured by St. George's respiratory questionnaire
Measured: 30 months
Correlation of plasma Growth and differentiation factor 15 levels with exercise tolerance
Exercise tolerance will be measured by six minute walk test
Measured: 30 months
Correlation of plasma Growth and differentiation factor levels 15 with physical activity levels
Physical activity will be measured by Sensewear armband
Measured: 30 months
Correlation of plasma Growth and differentiation factor levels 15 with echocardiographic measures of severity of pulmonary hypertension
Measured: 30 months
Correlation of GDF-15 levels in biopsy specimens with muscle wasting and weakness
Wasting will be measured by quadriceps cross sectional area and weakness will be defined by quadriceps maximal volitional capacity
Measured: 30 months
Determine the contribution of atrophy and autophagy to muscle wasting in PAH
Muscle biopsy specimens will be evaluated using microscopy and real time polymerase chain reaction
Measured: 30 months
Determine the contribution of SMAD and non-SMAD signalling pathways to the development of muscle weakness and wasting in PAH
Phosphorylation of SMAD and non-SMAD signalling will be determined by western blot
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2013 (estimated)
- Study startOct 2013
- Primary completionAug 2016
- Study completionAug 2016
Why it stopped: numbers recruited to show adequate association but not primary outcome
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Muscle WeaknessStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Other
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, Royal Brompton & Harefield NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Stephen J Wort, MBBS, Principal investigator, Imperial College / Royal Brompton Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01847716
- Sponsor's protocol ID
- 13IC0457
- Status last verified
- Sep 2018
- First submitted
- 19 Apr 2013
- Last updated
- 26 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Garfield BE, Crosby A, Shao D, Yang P, Read C, Sawiak S, Moore S, Parfitt L, Harries C, Rice M, Paul R, Ormiston ML, Morrell NW, Polkey MI, Wort SJ, Kemp PR. Growth/differentiation factor 15 causes TGFbeta-activated kinase 1-dependent muscle atrophy in pulmonary arterial hypertension. Thorax. 2019 Feb;74(2):164-176. doi: 10.1136/thoraxjnl-2017-211440. Epub 2018 Dec 15.
PubMed 30554141
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transforming Growth Factor Beta Signalling in the Development of Muscle Weakness in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01847716
- Acronym / sponsor ID
- 13IC0457
- Conditions
- Muscle Weakness, Pulmonary Arterial Hypertension
- Keywords
- Muscle weakness, Pulmonary arterial hypertension, Transforming growth factor beta, Growth and differentiation factor 15
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: numbers recruited to show adequate association but not primary outcome
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Medical Research Council, Royal Brompton & Harefield NHS Foundation Trust
- Study start
- Oct 2013
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 7 May 2013 (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.
Pulmonary arterial hypertension (PAH) is a disease that causes raised blood pressure in blood vessels that pick up oxygen from the lungs. It has a life expectancy similar to some cancers. There is treatment available but there is no cure. We now know that PAH is associated with weakness in the muscles in the legs, which contributes to the symptoms patients' experience. Researchers believe that certain proteins found in high levels in the blood of patients with other chronic diseases can affect muscle function and growth. One of these proteins is called growth differentiating factor (GDF) 8, high levels of which are associated with muscle weakness in chronic obstructive pulmonary disease(COPD) and heart failure (HF). Interestingly there are drugs available which block the actions of GDF-8 on muscle cells which has been shown in animals to result in increased muscle size. A related protein called GDF-15 is found in elevated levels in patients PAH, and is linked to prognosis. Our preliminary data suggests that GDF-15 can also directly influence muscle size in a number of situations. We aim to investigate the role of GDF-15 and related molecules in the development of muscle weakness in patients with PAH. We will do this by measuring certain markers of muscle weakness and taking blood and muscle samples in patients and controls. We will then compare the levels of GDF-15 in these tissues in those with and without muscle wasting. We hope this work will lead to a greater understanding of the role of GDF-15 in the development of muscle weakness in patients with PAH. GDF-15 levels may be important in allowing us to define which patients have muscle weakness. In the future we aim to perform a clinical trial of drugs which block the actions of GDF-15.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PH with wasting | – | –This group of patients with idiopathic pulmonary arterial hypertension exhibit quadriceps wasting |
| PH no wasting | – | –This groups of patients with idiopathic pulmonary arterial hypertension exhibit no evidence of muscle wasting |
| Controls | – | –This group of volunteers does not have pulmonary arterial hypertension and would not be expected to have muscle wasting |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Clinics at Royal Brompton and Hammersmith hospital
Key inclusion criteria (1 listed)
- Patients with pulmonary arterial hypertension with New York Heart Association stage II - III disease will be eligible for recruitment in the patient portion of the trial. Interested healthy age matched volunteers will also be recruited.
Key exclusion criteria (1 listed)
- Patients and volunteers will be excluded if they have significant co-morbidities including other cardiorespiratory disease, metabolic abnormalities including diabetes or thyroid disorders. They will be excluded if they cannot safely exercise and perform a six minute walk test or if they are wheelchair bound.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Plasma growth and differentiation factor 15 levels in participants with and without muscle wasting
Time frame: 30 months
Muscle wasting will be defined by quadriceps cross sectional area measured by ultrasound
12 secondary outcomes
Correlation of plasma Growth and differentiation factor 15 levels with muscle strength
Time frame: 30 months
Change in fibre type in muscle biopsy
Time frame: 30 months
GDF-15 levels in biopsy specimens
Time frame: 30 months
Correlation of plasma Growth and differentiation factor 15 levels with brain natriuretic protein levels
Time frame: 30 months
Correlation of plasma Growth and differentiation factor 15 levels with fat free mass index
Time frame: 30 months
Correlation of plasma Growth and differentiation factor 15 levels with quality of life
Time frame: 30 months
Correlation of plasma Growth and differentiation factor 15 levels with exercise tolerance
Time frame: 30 months
Correlation of plasma Growth and differentiation factor levels 15 with physical activity levels
Time frame: 30 months
Correlation of plasma Growth and differentiation factor levels 15 with echocardiographic measures of severity of pulmonary hypertension
Time frame: 30 months
Correlation of GDF-15 levels in biopsy specimens with muscle wasting and weakness
Time frame: 30 months
Determine the contribution of atrophy and autophagy to muscle wasting in PAH
Time frame: 30 months
Determine the contribution of SMAD and non-SMAD signalling pathways to the development of muscle weakness and wasting in PAH
Time frame: 30 months
Results and safety
The study was stopped early (reason given: numbers recruited to show adequate association but not primary outcome). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2018.
- Derived from this study: PubMed 30554141Garfield BE, Crosby A, Shao D, Yang P, Read C, Sawiak S, Moore S, Parfitt L, Harries C, Rice M, Paul R, Ormiston ML, Morrell NW, Polkey MI, Wort SJ, Kemp PR. Growth/differentiation factor 15 causes TGFbeta-activated kinase 1-dependent muscle atrophy in pulmonary arterial hypertension. Thorax. 2019 Feb;74(2):164-176. doi: 10.1136/thoraxjnl-2017-211440. Epub 2018 Dec 15.
- Individual participant dataSharing planned: Undecided
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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.
Stephen J Wort, MBBS principal investigator
Imperial College / Royal Brompton Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Muscle Weakness and Pulmonary Arterial Hypertension, run by Imperial College London at 1 site 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?
The sponsor lists 1 inclusion and 1 exclusion criteria. 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: stopped early, as of the sponsor's last update on 26 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 stopped early (reason given: numbers recruited to show adequate association but not primary outcome). Results are not available in the source record.
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?
Plasma growth and differentiation factor 15 levels in participants with and without muscle wasting (time frame: 30 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01847716, which also lists 1 linked publication.
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 26 Sep 2018.