search
Back to results

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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Unknown status
Phase
Early Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
d-cycloserine
placebo
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Chronic Obstructive Pulmonary Disease focused on measuring dyspnea, fmri, d-cycloserine

Eligibility Criteria

45 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • Oxford Centre for Clinical Magnetic Resonance ImagingRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Drug: d-cycloserine or placebo

D-cycloserine

Arm Description

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

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

Outcomes

Primary Outcome Measures

BOLD signal changes
Changes in FMRI BOLD signal in response to breathlessness cues, as a consequence of d-cycloserine administration during pulmonary rehabilitation.

Secondary Outcome Measures

Grey matter volume
Change in regional brain volume related to changes in breathlessness as a consequence of d-cycloserine administration during pulmonary rehabilitation.

Full Information

First Posted
October 29, 2013
Last Updated
October 11, 2018
Sponsor
University of Oxford
Collaborators
National Health Service, United Kingdom
search

1. Study Identification

Unique Protocol Identification Number
NCT01985750
Brief Title
Understanding the Importance of Plasticity in the Brain Mechanisms of Dyspnoea Perception
Official Title
Understanding the Importance of Plasticity in the Brain Mechanisms of Dyspnoea Perception
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Unknown status
Study Start Date
November 2013 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
February 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
National Health Service, United Kingdom

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
dyspnea, fmri, d-cycloserine

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Drug: d-cycloserine or placebo
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
D-cycloserine
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
d-cycloserine
Other Intervention Name(s)
comparison of d-cycloserine or placebo on enhancing the beneficial effects of pulmonary rehabilitation on breathlessness perception
Intervention Description
250mg d-cycloserine or identical placebo given immediately to the first 4 sessions of a 6-week course pulmonary rehabilitation.
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
Placebo - identically matched to d-cycloserine containing carrier compound only
Intervention Description
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
Primary Outcome Measure Information:
Title
BOLD signal changes
Description
Changes in FMRI BOLD signal in response to breathlessness cues, as a consequence of d-cycloserine administration during pulmonary rehabilitation.
Time Frame
baseline, week 3, week 8, 3 months following treatment
Secondary Outcome Measure Information:
Title
Grey matter volume
Description
Change in regional brain volume related to changes in breathlessness as a consequence of d-cycloserine administration during pulmonary rehabilitation.
Time Frame
baseline, week 3, week 8, 3 months following treatment
Other Pre-specified Outcome Measures:
Title
Grey matter volume compared with healthy controls
Description
Difference in regional brain volume related to breathlessness in comparison with healthy controls.
Time Frame
baseline, week 3, week 8, 3 months following treatment
Title
difference in BOLD signal compared with healthy controls
Description
Difference in FMRI BOLD signal in response to breathlessness cues, in comparison with healthy controls.
Time Frame
baseline, week 3, week 8, 3 months following treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kyle TS Pattinson, BM DPhil FRCA
Phone
01865 231 509
Email
kyle.pattinson@nda.ox.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Finnegan, DPhil
Phone
01865 234 544
Email
copd@fmrib.ox.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kyle TS Pattinson, BM DPhil FRCA
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oxford Centre for Clinical Magnetic Resonance Imaging
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kyle Pattinson, BM DPhil FRCA
Phone
+441865 231509
Email
kyle.pattinson@nda.ox.ac.uk
First Name & Middle Initial & Last Name & Degree
Sarah Finnegan, DPhil
Phone
+441865 234544
Email
copd@fmrib.ox.ac.uk

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs