Trial record 16 of 1335 for:    hypertension | Open Studies | Exclude Unknown

Transforming Growth Factor Beta Signalling in the Development of Muscle Weakness in Pulmonary Arterial Hypertension

This study is currently recruiting participants.
Verified April 2013 by Imperial College London
Sponsor:
Collaborators:
Medical Research Council
Royal Brompton & Harefield NHS Foundation Trust
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01847716
First received: April 19, 2013
Last updated: November 26, 2013
Last verified: April 2013
  Purpose

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.


Condition
Muscle Weakness
Pulmonary Arterial Hypertension

Study Type: Observational
Study Design: Observational Model: Cohort
Official Title: Transforming Growth Factor Beta Signalling in the Development of Muscle Weakness in Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Plasma growth and differentiation factor 15 levels in participants with and without muscle wasting [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Muscle wasting will be defined by quadriceps cross sectional area measured by ultrasound


Secondary Outcome Measures:
  • Correlation of plasma Growth and differentiation factor 15 levels with muscle strength [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Muscle strength will be measured by quadriceps maximal volitional capacity percent predicted

  • Change in fibre type in muscle biopsy [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • GDF-15 levels in biopsy specimens [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • Correlation of plasma Growth and differentiation factor 15 levels with brain natriuretic protein levels [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • Correlation of plasma Growth and differentiation factor 15 levels with fat free mass index [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Fat free mass index will be measured by bioelectrical impedence

  • Correlation of plasma Growth and differentiation factor 15 levels with quality of life [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Quality of life will be measured by St. George's respiratory questionnaire

  • Correlation of plasma Growth and differentiation factor 15 levels with exercise tolerance [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Exercise tolerance will be measured by six minute walk test

  • Correlation of plasma Growth and differentiation factor levels 15 with physical activity levels [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Physical activity will be measured by Sensewear armband

  • Correlation of plasma Growth and differentiation factor levels 15 with echocardiographic measures of severity of pulmonary hypertension [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • Correlation of GDF-15 levels in biopsy specimens with muscle wasting and weakness [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Wasting will be measured by quadriceps cross sectional area and weakness will be defined by quadriceps maximal volitional capacity

  • Determine the contribution of atrophy and autophagy to muscle wasting in PAH [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Muscle biopsy specimens will be evaluated using microscopy and real time polymerase chain reaction

  • Determine the contribution of SMAD and non-SMAD signalling pathways to the development of muscle weakness and wasting in PAH [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Phosphorylation of SMAD and non-SMAD signalling will be determined by western blot


Biospecimen Retention:   Samples With DNA

Muscle biopsy and blood specimens will be retained by Imperial College and are subject to thier restrictions ad regulations


Estimated Enrollment: 93
Study Start Date: October 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Clinics at Royal Brompton and Hammersmith hospital

Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01847716

Contacts
Contact: Benjamin E Garfield, MSc, BMBS, BMedSci 07947242984 b.garfield@imperial.ac.uk
Contact: Stephen J Wort, MA, MBBS, PhD 020 7351 8528 s.wort@imperial.ac.uk

Locations
United Kingdom
Royal Brompton Hospital Recruiting
London, United Kingdom, SW36NP
Contact: Benjamin Garfield, BMBS    02083528121    b.garfield@rbht.nhs.uk   
Sub-Investigator: Benjamin Garfield, BMBS         
Sponsors and Collaborators
Imperial College London
Medical Research Council
Royal Brompton & Harefield NHS Foundation Trust
Investigators
Principal Investigator: Stephen J Wort, MBBS Imperial College / Royal Brompton Hospital
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01847716     History of Changes
Other Study ID Numbers: 13IC0457
Study First Received: April 19, 2013
Last Updated: November 26, 2013
Health Authority: United Kingdom: National Institute for Health Research

Keywords provided by Imperial College London:
Muscle weakness
Pulmonary arterial hypertension
Transforming growth factor beta
Growth and differentiation factor 15

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Asthenia
Muscle Weakness
Paresis
Signs and Symptoms
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014