Chronic Obstructive Pulmonary DiseaseEarly Phase 1NCT01985750
Understanding the Importance of Plasticity in the Brain Mechanisms of Dyspnoea Perception
A Early Phase 1 study testing d-cycloserine in people with Chronic Obstructive Pulmonary Disease, run by University of Oxford at 1 site in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 45 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- d-cycloserine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2013to Feb 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Oxford Centre for Clinical Magnetic Resonance Imaging
Oxford, Oxfordshire, OX3 9DU
Kyle Pattinson, BM DPhil FRCA, +441865 231509, kyle.pattinson@nda.ox.ac.uk
Sarah Finnegan, DPhil, +441865 234544, copd@fmrib.ox.ac.uk
About 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.
Read more
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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- d-cycloserine, placebo
- Keywords
- dyspnea, fmri, d-cycloserine
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Dyspnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
d-cycloserineDrug
Also called 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.
placeboDrug
Also called Placebo - identically matched to d-cycloserine containing carrier compound only
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 group | Role | What they receive |
|---|---|---|
| Drug: d-cycloserine or placebo | Placebo comparator | 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 Receives: Drug: placebo |
| D-cycloserine | Active comparator | 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 Receives: Drug: d-cycloserine |
What is being measured
The primary outcome is the main question the study is designed to answer.
BOLD signal changes
Changes in FMRI BOLD signal in response to breathlessness cues, as a consequence of d-cycloserine administration during pulmonary rehabilitation.
Measured: baseline, week 3, week 8, 3 months following treatment
Secondary outcomes (1)
Grey matter volume
Change in regional brain volume related to changes in breathlessness as a consequence of d-cycloserine administration during pulmonary rehabilitation.
Measured: baseline, week 3, week 8, 3 months following treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2013 (estimated)
- Study startNov 2013
- Primary completionDec 2018 (estimated)
- Study completionFeb 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- National Health Service, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Kyle TS Pattinson, BM DPhil FRCA, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01985750
- Sponsor's protocol ID
- OX-KP001
- Status last verified
- Oct 2018
- First submitted
- 29 Oct 2013
- Last updated
- 12 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Finnegan SL, Harrison OK, Ezra M, Harmer CJ, Nichols TE, Rahman NM, Reinecke A, Pattinson KTS. The effect of D-cycloserine on brain connectivity over a course of pulmonary rehabilitation - A randomised control trial with neuroimaging endpoints. PLoS One. 2025 Jun 2;20(6):e0323213. doi: 10.1371/journal.pone.0323213. eCollection 2025.
PubMed 40455920Finnegan SL, Harrison OK, Booth S, Dennis A, Ezra M, Harmer CJ, Herigstad M, Guillaume B, Nichols TE, Rahman NM, Reinecke A, Renaud O, Pattinson KTS. The effect of d-cycloserine on brain processing of breathlessness over pulmonary rehabilitation: an experimental medicine study. ERJ Open Res. 2023 Apr 3;9(2):00479-2022. doi: 10.1183/23120541.00479-2022. eCollection 2023 Mar.
PubMed 37020840Finnegan SL, Browning M, Duff E, Harmer CJ, Reinecke A, Rahman NM, Pattinson KTS. Brain activity measured by functional brain imaging predicts breathlessness improvement during pulmonary rehabilitation. Thorax. 2023 Sep;78(9):852-859. doi: 10.1136/thorax-2022-218754. Epub 2022 Dec 26.
PubMed 36572534
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding the Importance of Plasticity in the Brain Mechanisms of Dyspnoea Perception
- ClinicalTrials.gov ID
- NCT01985750
- Acronym / sponsor ID
- OX-KP001
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- dyspnea, fmri, d-cycloserine
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- National Health Service, United Kingdom
- Study start
- Nov 2013
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Feb 2020 (estimated)
- First posted
- 15 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Drug: d-cycloserine or placebo | Placebo comparator | 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 |
| D-cycloserine | Active comparator | Drug: 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 |
Who may qualify
- Ages
- 45 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| d-cycloserineAlso: comparison of d-cycloserine or placebo on enhancing the beneficial effects of pulmonary rehabilitation on breathlessness perception250mg d-cycloserine or identical placebo given immediately to the first 4 sessions of a 6-week course pulmonary rehabilitation. | Drug | D-cycloserine |
| placeboAlso: Placebo - identically matched to d-cycloserine containing carrier compound onlyOther 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 | Drug: d-cycloserine or placebo |
Primary outcome
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.
1 secondary outcome
Grey matter volume
Time frame: baseline, week 3, week 8, 3 months following treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2018.
- Derived from this study: PubMed 40455920Finnegan SL, Harrison OK, Ezra M, Harmer CJ, Nichols TE, Rahman NM, Reinecke A, Pattinson KTS. The effect of D-cycloserine on brain connectivity over a course of pulmonary rehabilitation - A randomised control trial with neuroimaging endpoints. PLoS One. 2025 Jun 2;20(6):e0323213. doi: 10.1371/journal.pone.0323213. eCollection 2025.
- Derived from this study: PubMed 37020840Finnegan SL, Harrison OK, Booth S, Dennis A, Ezra M, Harmer CJ, Herigstad M, Guillaume B, Nichols TE, Rahman NM, Reinecke A, Renaud O, Pattinson KTS. The effect of d-cycloserine on brain processing of breathlessness over pulmonary rehabilitation: an experimental medicine study. ERJ Open Res. 2023 Apr 3;9(2):00479-2022. doi: 10.1183/23120541.00479-2022. eCollection 2023 Mar.
- Derived from this study: PubMed 36572534Finnegan SL, Browning M, Duff E, Harmer CJ, Reinecke A, Rahman NM, Pattinson KTS. Brain activity measured by functional brain imaging predicts breathlessness improvement during pulmonary rehabilitation. Thorax. 2023 Sep;78(9):852-859. doi: 10.1136/thorax-2022-218754. Epub 2022 Dec 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kyle TS Pattinson, BM DPhil FRCA principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing d-cycloserine in people with Chronic Obstructive Pulmonary Disease, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kyle TS Pattinson, BM DPhil FRCA (01865 231 509, kyle.pattinson@nda.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BOLD signal changes (time frame: baseline, week 3, week 8, 3 months following treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01985750, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2018.