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Chronic Obstructive Pulmonary Disease | Understanding the Importance of Plasticity in the Brain Mechanisms of Dyspnoea Perception

Chronic Obstructive Pulmonary Disease research study

What is the primary objective of this study?

Dyspnoea is the uncomfortable shortness of breath that debilitates millions of patients with lung disease, heart failure and cancer. It is often very difficult to treat. The sensations of dyspnoea are processed in the brain, and we believe that psychological factors modify and amplify these sensations, frequently exacerbating symptoms. This study aims to identify the importance of learning in the brain mechanisms of dyspnoea by investigating a cohort of patients with chronic breathlessness undergoing pulmonary rehabilitation . Pulmonary rehabilitation is a six-week course of exercise, education and group therapy that improves dyspnoea but does not improve lung function. This leads us to hypothesise that some of the beneficial effects of PR maybe due to changes in brain processing, potentially relating to a learning effect. Therefore to probe whether learning is important in the beneficial effects of pulmonary rehabilitation, we intend to modify learning with the drug d-cycloserine. D-cycloserine is an antibiotic that enhances learning due to its effects at N-methyl D-aspartate (NMDA) receptors in the hippocampus. Our previous study in a similar group of patients demonstrated the importance of the hippocampus in breathlessness perception, and we now wish to investigate this in more depth. The study involves collecting physiological, psychological and clinical measures on in conjunction with brain scanning, before, during and once after pulmonary rehabilitation. Subjects will either receive d-cyloserine or placebo before the first four pulmonary rehabilitation sessions.

Who is eligible to participate?

Inclusion Criteria: - Males and females with chronic lung disease, aged between 45 and 85 years old who have been referred for pulmonary rehabilitation. - The subject is able and willing to give fully informed consent. Exclusion Criteria: Any of the commonly accepted contraindications to MRI scanning, for example, severe claustrophobia, presence of metallic implants, a pacemaker etc. - Pregnancy. The risk to foetus of radiofrequency energy of the MRI scan is unknown. - Inadequate understanding of verbal and written information in English, sufficient to complete an MRI safety screening. - Unable to lie flat and still for 1/2 hour - Requirements for oxygen therapy - Significant cardiac, neurological, psychiatric or metabolic disease - Contra-indications to d-cycloserine: Alcoholism, known hypersensitivity, severe renal failure - Regular therapy with prescribed opioid analgesics - Antidepressant therapy (this may alter hippocampal plasticity) - Previous pulmonary rehabilitation (because the learning may be different on repeat pulmonary rehabilitation treatments)

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Chronic Obstructive Pulmonary Disease

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:d-cycloserine250mg d-cycloserine or identical placebo given immediately to the first 4 sessions of a 6-week course pulmonary rehabilitation.

Drug:placeboOther Names: comparison of d-cycloserine or placebo on enhancing the beneficial effects of pulmonary rehabilitation on breathlessness perception 250mg d-cycloserine or identical placebo given immediately to the first 4 sessions of a 6-week course pulmonary rehabilitation

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Drug: d-cycloserine or placeboOther Names: comparison of d-cycloserine or placebo on enhancing the beneficial effects of pulmonary rehabilitation on breathlessness perception 250mg d-cycloserine or identical placebo given immediately to the first 4 sessions of a 6-week course pulmonary rehabilitation

D-cycloserinePlacebo Comparator: Drug: d-cycloserine or placebo Other Names: comparison of d-cycloserine or placebo on enhancing the beneficial effects of pulmonary rehabilitation on breathlessness perception 250mg d-cycloserine or identical placebo given immediately to the first 4 sessions of a 6-week course pulmonary rehabilitation

Study Status

Recruiting

Start Date: November 2013

Completed Date: December 2017

Phase: Early Phase 1

Type: Interventional

Design:

Primary Outcome: BOLD signal changes

Secondary Outcome: Grey matter volume

Study sponsors, principal investigator, and references

Principal Investigator: Kyle TS Pattinson, BM DPhil FRCA

Lead Sponsor: University of Oxford

Collaborator: National Health Service, United Kingdom

More information:https://clinicaltrials.gov/show/NCT01985750

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