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

October 11, 2018 updated by: University of Oxford

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

90

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 9DU
        • Recruiting
        • Oxford Centre for Clinical Magnetic Resonance Imaging
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • comparison of d-cycloserine or placebo on enhancing the beneficial effects of pulmonary rehabilitation on breathlessness perception

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
baseline, week 3, week 8, 3 months following treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
baseline, week 3, week 8, 3 months following treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
baseline, week 3, week 8, 3 months following treatment
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.
baseline, week 3, week 8, 3 months following treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

National Health Service, United Kingdom

Investigators

  • Principal Investigator: Kyle TS Pattinson, BM DPhil FRCA, University of Oxford

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (ANTICIPATED)

December 1, 2018

Study Completion (ANTICIPATED)

February 1, 2020

Study Registration Dates

First Submitted

October 29, 2013

First Submitted That Met QC Criteria

November 8, 2013

First Posted (ESTIMATE)

November 15, 2013

Study Record Updates

Last Update Posted (ACTUAL)

October 12, 2018

Last Update Submitted That Met QC Criteria

October 11, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OX-KP001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Obstructive Pulmonary Disease

Clinical Trials on placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mozambique

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe