Clinical trial NCT06100068: HOBBIT 3: Mental Exercises and Temporal Alteration
Official title: Hyperventilation and Oxygenation to Increase Breath Hold in Breast Cancer Irradiation Treatment (HOBBIT) 3: Mental Exercises and Temporal Alteration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Neoplasm
Radiotherapy
Breath Holding
Mental Test
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2023-10-25
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: In the HOBBIT-trial by Vakaet et al. A protocol was developed to increase breath-hold time using (voluntary) hyperventilation and oxygenation to achieve DIBH times around 3 minutes.

Multiple non-medical interventions are being investigated to prolong a L-DIBH that are feasible in clinical practice. One of these methods will be to alter the time perception of the subjects. It has been noted in multiple studies (both medical and not) that slowing a person's perception of time results in an increase in breath-hold time. This alteration in time perception can be achieved with the use of a slowed clock as well as the usage of mental or physical exercises to preoccupy the subjects.

Volunteers will then be randomised into either the standard arm or the intervention arm. The intervention arm will follow standard protocol regarding DIBH preparation, though during the L-DIBH they will be asked to perform a simple mental exercise on a tablet. After 2 sessions of 3 L-DIBHs each, there will be a cross-over to the other arm in order to ascertain comfort and preference with each technique.

Detailed description: Adjuvant radiation therapy has a well-established role in the treatment of breast cancer complementing surgery and systemic treatment, improving survival and local control in both local and regional disease. The long-term follow-up, however, does show increased cardiac morbidity and mortality. The risk of heart disease is greatest in patients receiving a higher heart dosage i.e., left sided breast cancer and irradiation of the internal mammary lymph nodes and does not appear to have a threshold. Lowering heart dose can be achieved by improved planning methods as well as increasing the distance between the target volume and the heart. A deep inspiration breath-hold (DIBH) is often used to this end.

An unassisted DIBH is between 12 and 30 seconds; a simple breast irradiation averages 4 DIBHS for completion. More advanced radiotherapy plans (including lymph nodes) needs up to 20 DIBHs. This great amount is both physically and mentally exhausting.

A protocol was developed to increase breath-hold time using (voluntary) hyperventilation and oxygenation to achieve DIBH times around 3 minutes.

Multiple non-medical interventions are being investigated to prolong a L-DIBH that are feasible in clinical practice. One of these methods will be to alter the time perception of the subjects. It has been noted in multiple studies (both medical and not) that slowing a person's perception of time results in an increase in breath-hold time. This alteration in time perception can be achieved with the use of a slowed clock as well as the usage of mental or physical exercises to preoccupy the subjects.

Other important factors on the duration of breath holds are stress and anxiety, which may also be influenced by (relaxation) exercises (including Abdominal breathing).

The standard protocol for the first phase will be based on the results of the original HOBBIT trial.

40 Volunteers will be asked to perform 3 L-DIBHs each preceded by 3 minutes of hyperventilation at 16 breaths/min with 40L/min at FiO2 60%.

Volunteers will then be randomised into either the standard arm or the intervention arm. The intervention arm will follow standard protocol regarding DIBH preparation, though during the L-DIBH they will be asked to perform a simple mental exercise on a tablet.

Data regarding L-DIBH time, side-effects and volunteer reported stress and comfort will be reported.

Volunteers in each group will be asked to perform 2 series of 3 L-DIBHs on 2 separate days. After having finished these 2 series, there will be a cross-over to the other arm. This cross-over will evaluate the known effect of the learning bias that we see with breath-hold and show whether this effect has an impact on the anticipated benefit of the intervention. With the cross-over we can also ascertain volunteer comfort and preference with each the technique.

Eligibility criteria: Inclusion Criteria:

* Volunteer
* Karnofsky index of at least 90
* Able to perform a single DIBH of at least twenty seconds without assistance
* Age ≥ 18 years
* Informed consent obtained, signed and dated before specific protocol procedures
* Female

Exclusion Criteria:

* Pregnant women
* Volunteers above WHO Obesity class II (BMI\>35kg/m²)
* Subjects on oxygen treatment during day or night
* COPD or Asthma patients
* Volunteers with pulmonary hypertension
* Gastric tube present
* Smoking
* Previous and substantial breath-holding experience in the past year (e.g., diver, etc.)
* Mental condition rendering the volunteer unable to understand the nature, scope and possible consequences of the study

Primary outcomes:
measure: Difference in average L-DIBH time between standard and experimental L-DIBH
timeFrame: 1 year
Secondary outcomes:
measure: Patient reported comfort
timeFrame: 1 year
measure: Patient preferece for standard or experimental L-DIBH setup
timeFrame: 1 year
measure: Average L-DIBH time
timeFrame: 1 year
measure: Median L-DIBH time
timeFrame: 1 year
measure: Minimum and Maximum L-DIBH time
timeFrame: 1 year
measure: Oxygen Saturation
timeFrame: 1 year
measure: Heart Rate
timeFrame: 1 year
measure: Patient report Pain
timeFrame: 1 year
measure: Correctness of the mental exercise
timeFrame: 1 year
Other outcomes:
measure: Breath-Hold related side-effects
timeFrame: 1 year
Locations:
city: Ghent
country: Belgium
facility: University Hospital - Radiotherapy Department
Study officials:
References:
citation: Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707-16. doi: 10.1016/S0140-6736(11)61629-2. Epub 2011 Oct 19.
citation: Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013 Mar 14;368(11):987-98. doi: 10.1056/NEJMoa1209825.
citation: Vakaet V, Van Hulle H, Schoepen M, Van Caelenberg E, Van Greveling A, Holvoet J, Monten C, De Baerdemaeker L, De Neve W, Coppens M, Veldeman L. Prolonging deep inspiration breath-hold time to 3 min during radiotherapy, a simple solution. Clin Transl Radiat Oncol. 2021 Feb 23;28:10-16. doi: 10.1016/j.ctro.2021.02.007. eCollection 2021 May.
citation: Schwarz MA, Winkler I, Sedlmeier P. The heart beat does not make us tick: the impacts of heart rate and arousal on time perception. Atten Percept Psychophys. 2013 Jan;75(1):182-93. doi: 10.3758/s13414-012-0387-8.
citation: Vigran HJ, Kapral AG, Tytell ED, Kao MH. Manipulating the perception of time affects voluntary breath-holding duration. Physiol Rep. 2019 Dec;7(23):e14309. doi: 10.14814/phy2.14309.