Breathlessness Patterns in Patients With Cancer, COPD and Heart Failure: an fMRI Feasibility Study

NCT ID: NCT07319039

Last Updated: 2026-01-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

16 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-08-26

Study Completion Date

2027-03-01

Brief Summary

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Dyspnea that persists despite optimal pathophysiological treatment is defined as persistent dyspnea.

Currently all brain functional magnetic resonance imaging (fMRI) studies conducted to evaluate breathlessness have done so using healthy volunteers or have concentrated on acute breathlessness. Little is known about chronic breathlessness patterns and their modulation by different triggers. Furthermore, it is currently assumed in the palliative care literature that patients suffering from different advanced and progressive diseases such as cancer, heart failure (HF) or chronic obstructive pulmonary disease (COPD) have the same triggers, perceptions and neurological pathways and thus require the same treatments/interventions (i.e. opioids as first line symptomatic pharmacologic treatment). However, it is now known that patients belonging to different disease groups do not necessarily benefit from opioids.

Aim of the study To assess the feasibility of identifying dyspnea patterns in different life-limiting conditions and to evaluate the effect of immersive virtual reality (IVR) on dyspnea using patient-reported-outcomes (PROMs).

Study procedure:

Patients with advanced chronic diseases such as cancer, COPD or HF suffering from dyspnea will undergo a brain fMRI in combination with an IVR intervention. The fMRI data will be reviewed to identify different patterns of dyspnea and the effect of IVR on dyspnea will be assessed through PROMs. Patients will be asked about the perceived burden of the study.

Detailed Description

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Dyspnea that persists despite optimal pathophysiologic treatment is defined as persistent dyspnea.

Breathlessness, also defined as dyspnea, is a frequent symptom in patients with advanced and progressive diseases such as cancer, chronic obstructive pulmonary disease (COPD) and advanced heart failure (HF). In affected patients, breathlessness causes substantial suffering and is a major contributor to decreased quality of life.

Despite increasingly controversial data on the effectiveness of opioids in advanced disease, they are often prescribed according to expert opinion. It can be hypothesized that breathlessness is conveyed by a variety of different pathophysiologies resulting in various patterns of the central nervous system (CNS) signalling, requiring more than a one-size-fits-all answer to pharmacologic interventions (i.e. opioids).

In recent years, the healthcare industry has seen the development of immersive virtual reality therapies (IVR), also called "digital therapeutics". Immersive virtual reality is an interactive computer simulation that allows a person to be completely immersed within a three-dimensional virtual environment so that it has a real feeling of being in the virtual world. IVR has been used during magnetic resonance imaging (MRI), to reduce stress and anxiety perceived by patients who suffer from claustrophobia.

Functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. Studies conducted to evaluate breathlessness have done so using healthy volunteers, focusing on acute breathlessness or in the context of pulmonary rehabilitation. Little is known about persistent breathlessness patterns and their modulation by different triggers.

Aim of the study:

It is possible that breathlessness is experienced and centrally processed in different ways between different patients, related to: i) the underlying disease, ii) the triggers for breathlessness episodes, iii) differences in patient-reported multidimensional assessment items (i.e. perceived severity vs discomfort vs effort). This study aims to assess whether different patterns of breathlessness can be identified by fMRI technology.

Hypothesis:

The investigators hypothesize that it is possible for patients suffering from persistent breathlessness associated with COPD, heart failure and incurable and life-limiting cancer to undergo an fMRI and associated study interventions.

Primary objective:

To determine the feasibility and acceptability of an observational monocentric study using fMRI and IVR in breathlessness patients with COPD, heart failure and cancer.

Secondary objective:

To identify different breathlessness fMRI signals in different diseases (COPD, heart failure, cancer) and identify different types of breathlessness patterns using fMRI, IVR, and clinical parameters (including patient-reported-outcome measures (PROMs)).

Project design The investigators plan to conduct an observational study that involves the use of an fMRI and IVR. A feasibility study design was chosen because the included patients need particular consideration and the feasibility of the procedure (fMRI) needs to be evaluated.

Total number of participants: four patients with HF, four patients with COPD, four patients with cancer, four healthy volunteers.

Participants will be recruited at the outpatient palliative care clinic of the HUG (single center) on the basis of a screening of medical records of patients and the preverification of the inclusion and exclusion criteria mentioned above.

The healthy controls will be recruited from a convenience sampling of known healthy volunteers meeting the above criteria, from a similar age group, under no hierarchical influence from any member of the research team.

Conditions

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Chronic Obstructive Pulmonary Disease (COPD) Heart Failure Cancer Volunteers

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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Participants

Patients and healthy volunteers who will have a cerebral fMRI

Cerebral fMRI

Intervention Type OTHER

Neuroimaging data will be collected using a 3T Siemens Prisma MRI scanner (Prisma; Siemens, Erlangen, Germany) equipped with a 64-channel head coil. Functional T2\*-weighted images will be acquired during the resting-state protocol. The sequences used will be gradient-echo planar imaging. Additionally, a single-band reference volume will be obtained prior to the functional acquisition, using the same parameters but without multiband (MB) acceleration, to assist in functional realignment and masking. A whole-brain T1-weighted multi-echo MPRAGE scan will also be performed with 1 mm isotropic resolution. three echo images were combined using the root-mean-square method.

Immersive virtual reality

Intervention Type OTHER

In collaboration with HypnoVR (HypnoVR, Strasbourg, France), patients will subsequently be provided with a visual immersion in a virtual world along with a scripted hypnotic voice track. HypnoVR's solution is certified as a medical device and has been studied in various medical contexts. The program will be adapted to run on its own dedicated PC instead of a (non-MRI compatible) HMD. As described in this protocol, the PL and the patients can select from a predefined set of virtual environments and choose the preferred voice-over script.

Interventions

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Cerebral fMRI

Neuroimaging data will be collected using a 3T Siemens Prisma MRI scanner (Prisma; Siemens, Erlangen, Germany) equipped with a 64-channel head coil. Functional T2\*-weighted images will be acquired during the resting-state protocol. The sequences used will be gradient-echo planar imaging. Additionally, a single-band reference volume will be obtained prior to the functional acquisition, using the same parameters but without multiband (MB) acceleration, to assist in functional realignment and masking. A whole-brain T1-weighted multi-echo MPRAGE scan will also be performed with 1 mm isotropic resolution. three echo images were combined using the root-mean-square method.

Intervention Type OTHER

Immersive virtual reality

In collaboration with HypnoVR (HypnoVR, Strasbourg, France), patients will subsequently be provided with a visual immersion in a virtual world along with a scripted hypnotic voice track. HypnoVR's solution is certified as a medical device and has been studied in various medical contexts. The program will be adapted to run on its own dedicated PC instead of a (non-MRI compatible) HMD. As described in this protocol, the PL and the patients can select from a predefined set of virtual environments and choose the preferred voice-over script.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years and
* Followed by the outpatient palliative care clinic of the Geneva University Hospitals, Switzerland (HUG) and
* Breathlessness at rest \> 2 and \< 8 on the NRS (numeric rating scale 0 to 10) and
* Persistent breathlessness (persistent dyspnea for \> 3 weeks despite adequate and maximal medication according to the pathology) and
* In a stable clinical condition, i.e., without an episode of acute cardiac, respiratory, and/or neurological failure leading to hospitalization in the previous 4 weeks and
* Diagnosis of either HF stage NYHA III-IV, or COPD with dyspnea on the modified MRC scale grade 3-4, or oncological disease with primary or secondary pulmonary involvement


* Age ≥ 18 years and
* No respiratory symptoms: dyspnea, cough, wheezing and
* No known pulmonary, cardiac, or oncological disease and
* Smoking status \< 10 pack-years and
* No contraindication to fMRI (Appendix 3) and
* Ability to lie flat (supine position) and
* No diagnosed psychiatric illness (severe depression, severe anxiety, psychosis, other) or antipsychotic treatment deemed a contraindication for fMRI based on physician judgement and
* No neurological disorders according to neurological assessment, including diagnosed dementia (frontotemporal dementia, Alzheimer's disease, etc.), brain pathology (tumor, stroke, Parkinson's disease, etc.), or epilepsy and
* No claustrophobia, acrophobia, photophobia, severe hearing loss, and/or severe visual deficit and
* No contraindication to IVR (migraines, photosensitive epilepsy, vertigo)

Exclusion Criteria

* Breathlessness at rest ≥ 8 on the NRS (numeric rating scale 0 to 10)
* Contraindication to fMRI
* Inability to lie flat (supine position)
* Diagnosed psychiatric illness (severe depression, severe anxiety, psychosis, other) or antipsychotic treatment deemed a contraindication for fMRI based on physician judgement
* Neurological disorders according to neurological assessment, including diagnosed dementia (frontotemporal dementia, Alzheimer's disease, etc.), brain pathology (tumor, stroke, Parkinson's disease, etc.), or epilepsy
* Presence of claustrophobia, acrophobia, photophobia, severe hearing loss, and/or severe visual deficit
* Contraindication to IVR (migraines, photosensitive epilepsy, vertigo)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Geneva

OTHER

Sponsor Role lead

Responsible Party

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Lisa Hentsch

Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lisa Hentsch, Dr med

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Geneva

Locations

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Geneva University Hospitals

Geneva, Canton of Geneva, Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Lisa Hentsch, Dr med

Role: CONTACT

+41795531093

Ivan Guerreiro, Dr Med

Role: CONTACT

+41795533717

Facility Contacts

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Federica Bianchi, PhD

Role: primary

+41764947150

References

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Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002 Jan;15(1):273-89. doi: 10.1006/nimg.2001.0978.

Reference Type BACKGROUND
PMID: 11771995 (View on PubMed)

Smallwood NE, Pascoe A, Wijsenbeek M, Russell AM, Holland AE, Romero L, Ekstrom M. Opioids for the palliation of symptoms in people with serious respiratory illness: a systematic review and meta-analysis. Eur Respir Rev. 2024 Oct 9;33(174):230265. doi: 10.1183/16000617.0265-2023. Print 2024 Oct.

Reference Type BACKGROUND
PMID: 39384304 (View on PubMed)

Ekstrom M, Ferreira D, Chang S, Louw S, Johnson MJ, Eckert DJ, Fazekas B, Clark KJ, Agar MR, Currow DC; Australian National Palliative Care Clinical Studies Collaborative. Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial. JAMA. 2022 Nov 22;328(20):2022-2032. doi: 10.1001/jama.2022.20206.

Reference Type BACKGROUND
PMID: 36413230 (View on PubMed)

Finnegan 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.

Reference Type BACKGROUND
PMID: 36572534 (View on PubMed)

Yu L, De Mazancourt M, Hess A, Ashadi FR, Klein I, Mal H, Courbage M, Mangin L. Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease. Hum Brain Mapp. 2016 Aug;37(8):2736-54. doi: 10.1002/hbm.23205. Epub 2016 Apr 5.

Reference Type BACKGROUND
PMID: 27059277 (View on PubMed)

Nakarada-Kordic I, Reay S, Bennett G, Kruse J, Lydon AM, Sim J. Can virtual reality simulation prepare patients for an MRI experience? Radiography (Lond). 2020 Aug;26(3):205-213. doi: 10.1016/j.radi.2019.11.004. Epub 2019 Nov 28.

Reference Type BACKGROUND
PMID: 32052767 (View on PubMed)

Cataldo J, Collins S, Walker J, Shaw T. Use of virtual reality for MRI preparation and technologist education: A scoping review. J Med Imaging Radiat Sci. 2023 Mar;54(1):195-205. doi: 10.1016/j.jmir.2022.11.011. Epub 2022 Dec 30.

Reference Type BACKGROUND
PMID: 36588009 (View on PubMed)

Garcia-Palacios A, Hoffman HG, Richards TR, Seibel EJ, Sharar SR. Use of virtual reality distraction to reduce claustrophobia symptoms during a mock magnetic resonance imaging brain scan: a case report. Cyberpsychol Behav. 2007 Jun;10(3):485-8. doi: 10.1089/cpb.2006.9926.

Reference Type BACKGROUND
PMID: 17594277 (View on PubMed)

Kilic A, Brown A, Aras I, Hui R, Hare J, Hughes LD, McCracken LM. Using Virtual Technology for Fear of Medical Procedures: A Systematic Review of the Effectiveness of Virtual Reality-Based Interventions. Ann Behav Med. 2021 Oct 27;55(11):1062-1079. doi: 10.1093/abm/kaab016.

Reference Type BACKGROUND
PMID: 33821879 (View on PubMed)

Wang S, Lim SH, Aloweni FBAB. Virtual reality interventions and the outcome measures of adult patients in acute care settings undergoing surgical procedures: An integrative review. J Adv Nurs. 2022 Mar;78(3):645-665. doi: 10.1111/jan.15065. Epub 2021 Oct 10.

Reference Type BACKGROUND
PMID: 34633112 (View on PubMed)

O'Connor S, Mayne A, Hood B. Virtual Reality-Based Mindfulness for Chronic Pain Management: A Scoping Review. Pain Manag Nurs. 2022 Jun;23(3):359-369. doi: 10.1016/j.pmn.2022.03.013. Epub 2022 Apr 28.

Reference Type BACKGROUND
PMID: 35491349 (View on PubMed)

Gaertner J, Fusi-Schmidhauser T, Stock S, Siemens W, Vennedey V. Effect of opioids for breathlessness in heart failure: a systematic review and meta-analysis. Heart. 2023 Jun 26;109(14):1064-1071. doi: 10.1136/heartjnl-2022-322074.

Reference Type BACKGROUND
PMID: 36878671 (View on PubMed)

Morita T, Sakaguchi Y, Hirai K, Tsuneto S, Shima Y. Desire for death and requests to hasten death of Japanese terminally ill cancer patients receiving specialized inpatient palliative care. J Pain Symptom Manage. 2004 Jan;27(1):44-52. doi: 10.1016/j.jpainsymman.2003.05.001.

Reference Type BACKGROUND
PMID: 14711468 (View on PubMed)

Morelot-Panzini C, Adler D, Aguilaniu B, Allard E, Bautin N, Beaumont M, Blanc FX, Chenivesse C, Dangers L, Delclaux C, Demoule A, Devillier P, Didier A, Georges M, Housset B, Janssens JP, Laveneziana P, Laviolette L, Muir JF, Ninot G, Perez T, Peiffer C, Schmidt M, Similowski T, Straus C, Taille C, Van Den Broecke S, Roche N; dyspnoea working group of the Societe de Pneumologie de Langue Francaise. Breathlessness despite optimal pathophysiological treatment: on the relevance of being chronic. Eur Respir J. 2017 Sep 27;50(3):1701159. doi: 10.1183/13993003.01159-2017. Print 2017 Sep. No abstract available.

Reference Type BACKGROUND
PMID: 28954773 (View on PubMed)

Currow DC, Dal Grande E, Ferreira D, Johnson MJ, McCaffrey N, Ekstrom M. Chronic breathlessness associated with poorer physical and mental health-related quality of life (SF-12) across all adult age groups. Thorax. 2017 Dec;72(12):1151-1153. doi: 10.1136/thoraxjnl-2016-209908. Epub 2017 Mar 29.

Reference Type BACKGROUND
PMID: 28356419 (View on PubMed)

Parshall MB, Schwartzstein RM, Adams L, Banzett RB, Manning HL, Bourbeau J, Calverley PM, Gift AG, Harver A, Lareau SC, Mahler DA, Meek PM, O'Donnell DE; American Thoracic Society Committee on Dyspnea. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012 Feb 15;185(4):435-52. doi: 10.1164/rccm.201111-2042ST.

Reference Type BACKGROUND
PMID: 22336677 (View on PubMed)

Other Identifiers

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BREACH-fMRI

Identifier Type: -

Identifier Source: org_study_id

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