Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01985750
Recruitment Status : Recruiting
First Posted : November 15, 2013
Last Update Posted : October 12, 2018
Sponsor:
Collaborator:
National Health Service, United Kingdom
Information provided by (Responsible Party):
University of Oxford

Brief 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.


Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: d-cycloserine Drug: placebo Early Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Understanding the Importance of Plasticity in the Brain Mechanisms of Dyspnoea Perception
Study Start Date : November 2013
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Cycloserine

Arm Intervention/treatment
Placebo 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

Drug: 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

Other Name: Placebo - identically matched to d-cycloserine containing carrier compound only

Active Comparator: D-cycloserine

Placebo 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

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




Primary Outcome Measures :
  1. BOLD signal changes [ Time Frame: baseline, week 3, week 8, 3 months following treatment ]
    Changes in FMRI BOLD signal in response to breathlessness cues, as a consequence of d-cycloserine administration during pulmonary rehabilitation.


Secondary Outcome Measures :
  1. Grey matter volume [ Time Frame: baseline, week 3, week 8, 3 months following treatment ]
    Change in regional brain volume related to changes in breathlessness as a consequence of d-cycloserine administration during pulmonary rehabilitation.


Other Outcome Measures:
  1. Grey matter volume compared with healthy controls [ Time Frame: baseline, week 3, week 8, 3 months following treatment ]
    Difference in regional brain volume related to breathlessness in comparison with healthy controls.

  2. difference in BOLD signal compared with healthy controls [ Time Frame: baseline, week 3, week 8, 3 months following treatment ]
    Difference in FMRI BOLD signal in response to breathlessness cues, in comparison with healthy controls.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   45 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01985750


Contacts
Layout table for location contacts
Contact: Kyle TS Pattinson, BM DPhil FRCA 01865 231 509 kyle.pattinson@nda.ox.ac.uk
Contact: Sarah Finnegan, DPhil 01865 234 544 copd@fmrib.ox.ac.uk

Locations
Layout table for location information
United Kingdom
Oxford Centre for Clinical Magnetic Resonance Imaging Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Contact: Kyle Pattinson, BM DPhil FRCA    +441865 231509    kyle.pattinson@nda.ox.ac.uk   
Contact: Sarah Finnegan, DPhil    +441865 234544    copd@fmrib.ox.ac.uk   
Sponsors and Collaborators
University of Oxford
National Health Service, United Kingdom
Investigators
Layout table for investigator information
Principal Investigator: Kyle TS Pattinson, BM DPhil FRCA University of Oxford

Layout table for additonal information
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01985750    
Other Study ID Numbers: OX-KP001
First Posted: November 15, 2013    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018
Keywords provided by University of Oxford:
dyspnea
fmri
d-cycloserine
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Dyspnea
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Signs and Symptoms
Cycloserine
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action