Understanding the Importance of Plasticity in the Brain Mechanisms of Dyspnoea Perception

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

Understanding the Importance of Plasticity in the Brain Mechanisms of Dyspnoea Perception

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01985750
• Other study ID #: OX-KP001
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 2013
• Est. completion date: February 2020

Study information

• Verified date: October 2018
• Source: University of Oxford
• Contact: Kyle TS Pattinson, BM DPhil FRCA
• Phone: 01865 231 509
• Email: kyle.pattinson[@]nda.ox.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: February 2020
• Est. primary completion date: December 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Dyspnea
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• d-cycloserine
250mg d-cycloserine or identical placebo given immediately to the first 4 sessions of a 6-week course pulmonary rehabilitation.
• 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

Locations

Country	Name	City	State
United Kingdom	Oxford Centre for Clinical Magnetic Resonance Imaging	Oxford	Oxfordshire

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	National Health Service, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Grey matter volume compared with healthy controls	Difference in regional brain volume related to breathlessness in comparison with healthy controls.	baseline, week 3, week 8, 3 months following treatment
Other	difference in BOLD signal compared with healthy controls	Difference in FMRI BOLD signal in response to breathlessness cues, in comparison with healthy controls.	baseline, week 3, week 8, 3 months following treatment
Primary	BOLD signal changes	Changes in FMRI BOLD signal in response to breathlessness cues, as a consequence of d-cycloserine administration during pulmonary rehabilitation.	baseline, week 3, week 8, 3 months following treatment
Secondary	Grey matter volume	Change in regional brain volume related to changes in breathlessness as a consequence of d-cycloserine administration during pulmonary rehabilitation.	baseline, week 3, week 8, 3 months following treatment