- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01847716
Transforming Growth Factor Beta Signalling in the Development of Muscle Weakness in Pulmonary Arterial Hypertension
24 september 2018 uppdaterad av: Imperial College London
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.
Studieöversikt
Status
Avslutad
Betingelser
Studietyp
Observationell
Inskrivning (Faktisk)
33
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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London, Storbritannien, SW36NP
- Royal Brompton Hospital
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
16 år till 63 år (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Testmetod
Icke-sannolikhetsprov
Studera befolkning
Clinics at Royal Brompton and Hammersmith hospital
Beskrivning
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.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Observationsmodeller: Kohort
- Tidsperspektiv: Övrig
Kohorter och interventioner
Grupp / Kohort |
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PH with wasting
This group of patients with idiopathic pulmonary arterial hypertension exhibit quadriceps wasting
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PH no wasting
This groups of patients with idiopathic pulmonary arterial hypertension exhibit no evidence of muscle wasting
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Controls
This group of volunteers does not have pulmonary arterial hypertension and would not be expected to have muscle wasting
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Plasma growth and differentiation factor 15 levels in participants with and without muscle wasting
Tidsram: 30 months
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Muscle wasting will be defined by quadriceps cross sectional area measured by ultrasound
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30 months
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Correlation of plasma Growth and differentiation factor 15 levels with muscle strength
Tidsram: 30 months
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Muscle strength will be measured by quadriceps maximal volitional capacity percent predicted
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30 months
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Change in fibre type in muscle biopsy
Tidsram: 30 months
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30 months
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GDF-15 levels in biopsy specimens
Tidsram: 30 months
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30 months
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Correlation of plasma Growth and differentiation factor 15 levels with brain natriuretic protein levels
Tidsram: 30 months
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30 months
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Correlation of plasma Growth and differentiation factor 15 levels with fat free mass index
Tidsram: 30 months
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Fat free mass index will be measured by bioelectrical impedence
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30 months
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Correlation of plasma Growth and differentiation factor 15 levels with quality of life
Tidsram: 30 months
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Quality of life will be measured by St. George's respiratory questionnaire
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30 months
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Correlation of plasma Growth and differentiation factor 15 levels with exercise tolerance
Tidsram: 30 months
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Exercise tolerance will be measured by six minute walk test
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30 months
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Correlation of plasma Growth and differentiation factor levels 15 with physical activity levels
Tidsram: 30 months
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Physical activity will be measured by Sensewear armband
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30 months
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Correlation of plasma Growth and differentiation factor levels 15 with echocardiographic measures of severity of pulmonary hypertension
Tidsram: 30 months
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30 months
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Correlation of GDF-15 levels in biopsy specimens with muscle wasting and weakness
Tidsram: 30 months
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Wasting will be measured by quadriceps cross sectional area and weakness will be defined by quadriceps maximal volitional capacity
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30 months
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Determine the contribution of atrophy and autophagy to muscle wasting in PAH
Tidsram: 30 months
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Muscle biopsy specimens will be evaluated using microscopy and real time polymerase chain reaction
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30 months
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Determine the contribution of SMAD and non-SMAD signalling pathways to the development of muscle weakness and wasting in PAH
Tidsram: 30 months
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Phosphorylation of SMAD and non-SMAD signalling will be determined by western blot
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30 months
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Huvudutredare: Stephen J Wort, MBBS, Imperial College / Royal Brompton Hospital
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 oktober 2013
Primärt slutförande (Faktisk)
1 augusti 2016
Avslutad studie (Faktisk)
1 augusti 2016
Studieregistreringsdatum
Först inskickad
19 april 2013
Först inskickad som uppfyllde QC-kriterierna
2 maj 2013
Första postat (Uppskatta)
7 maj 2013
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
26 september 2018
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
24 september 2018
Senast verifierad
1 september 2018
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Patologiska processer
- Hjärt-kärlsjukdomar
- Kärlsjukdomar
- Sjukdomar i nervsystemet
- Luftvägssjukdomar
- Lungsjukdomar
- Neurologiska manifestationer
- Muskuloskeletala sjukdomar
- Muskelsjukdomar
- Neuromuskulära manifestationer
- Hypertoni, lung
- Hypertoni
- Muskelsvaghet
- Pulmonell arteriell hypertoni
- Familjär primär pulmonell hypertoni
- Pares
- Asteni
Andra studie-ID-nummer
- 13IC0457
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
Obeslutsam
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Muskelsvaghet
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University of AthensOkändCritical Illness Polyneuromyopati (CIPNM) | ICU Acquired Weakness (ICUAW)Grekland
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University Hospital Inselspital, BerneNestec Ltd.AvslutadMuskelsvaghet | Intensivvårdsavdelning (ICU) Acquired Weakness (ICU - AW)Schweiz