Clinical trial NCT03959735: High Intensity Interval Training in Severe Mental Illness
Official title: "Is the Use of High Intensity Interval Training (HIIT) Feasible and Acceptable Amongst Inpatients With Severe Mental Illness (SMI)?" A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder
Bipolar Disorder
Schizophrenia
Keywords: inpatients
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: South London and Maudsley NHS Foundation Trust
First posted: 2019-05-22
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Feasibility Randomized Controlled Trial (RCT)
Primary purpose: TREATMENT

Brief summary: People experiencing severe mental illnesses (SMI), including schizophrenia, psychosis, bipolar disorder and major depressive disorder, are prone to poorer physical health and increased incidences of premature mortality when compared to the general population (De Hert et al., 2009; Hert et al., 2011; Hennekens et al., 2005; Tiihonen et al., 2009 . High-intensity-interval-training (HIIT) is a type of exercise involving alternating short bursts of high intensity exercise with recovery periods of rest/ light exercise (Weston, Wisløff \& Coombes, 2014). HIIT improves physical health, quality of life and cognition in the general population and in those with physical health disorders (Gomes-Neto et al., 2017; Hwang, Wu \& Chou, 2011; Wen et al., 2019). It has been proposed that HIIT may improve symptoms, physical health and time to discharge among inpatients with SMI.

The research will involve three stages: 1) Focus groups, 2) A pilot study, 3) Follow-up qualitative interviews and focus groups.

Firstly, a series of focus groups with inpatients with SMI, carers of individuals with SMI and clinical staff will be conducted. The focus groups will scope perceptions of attitudes, and practicalities of a pilot RCT. The information gained will be used to inform a pilot HIIT trial which will evaluate whether HIIT is acceptable and feasible amongst this population group. Each focus group will run for ≈2 hours and will involve an open discussion about the benefits and barriers of conducting HIIT exercise sessions in a population with SMI.

Secondly, the HIIT pilot study will be trialed. The final protocol will be developed with feedback from the focus group but will involve an RCT where 12 weeks of HIIT will be compared to 12 weeks of treatment-as-usual (TAU). HIIT will be conducted, twice a week, in a supervised environment using a stationary bike. Inpatients with a diagnosis of SMI will be eligible to participate. Thirdly, follow-up qualitative interviews, with pilot study participants, those that withdrew and those that did not want to take part, and focus groups with clinical staff will address the acceptability and feasibility of HIIT.

Detailed description: Setting:

All three stages will take place in various South London and Maudsley Hospital NHS Trust (SLaM) Adult Mental Health settings affiliated with the Maudsley Hospital and the Bethlem Royal Hospital, and at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN).

Stage One:

A series of focus groups with inpatients with a diagnosis of SMI, carers of people with a diagnosis of SMI and clinical staff will scope perceptions of attitudes, and practicalities of a pilot RCT. It is expected that between 6-8 people will attend each focus group.

Up to 5 focus groups will be conducted, lasting two hours each, addressed at the following populations: 1) Clinical staff affiliated with SLaM; 2) Inpatients with a diagnosis of SMI who reside at the Maudsley Hospital and the Bethlem Royal Hospital, and their carers; 3) Carers recruited via the national carers' forum, a carers group in SLaM.

Procedure: A series of simple open-ended questions will be asked, and participants will answer verbally. The questions will address factors relevant to the pilot study design including optimal duration and intensity of exercise sessions; location of exercise sessions; procedures surrounding storage of exercise equipment; and procedure surrounding outcome assessments. An audio-recording will record responses to these questions when permission has been granted. The qualitative data gained from the questions asked as part of the focus group will be analysed using thematic analysis to understand the main themes.

Stage Two:

Part a- A pilot RCT will be conducted whereby inpatients with a diagnosis of SMI will be randomly allocated to either 12 weeks of HIIT or 12 weeks of TAU. For patients in the HIIT arm, HIIT will be conducted twice a week for 12 weeks using a stationary bike. Each session will have the following structure: 4-minute warm-up, followed by 5X1 minute intervals at 85-95% of maximum heart rate, interspersed with active pauses of 90 seconds cycling at approximately 60-70% of maximum heart rate, and a 4-minute cool-down. Assessment measures including a neuropsychological test battery; fitness test; and physical health checks will be conducted at baseline, 6-, and 12-weeks. Twenty inpatients will be recruited to each arm of the RCT (40 inpatients in total). This number is based on recruiting a big-enough sample to assess the feasibility of the study and on the resources available (Leon, Davis \& Kraemer, 2011).

Pre-post intervention changes in will be measured, including changes in neuropsychological outcomes, fitness, physical health, and cardiovascular risk. A between-group analysis will also be conducted to see whether any changes in outcome differ from the control (TAU) group.

Part b- The RCT commenced in January 2020 using the above RCT procedure. Recruitment was halted in March 2020 at the start of the Covid-19 pandemic and HIIT sessions were ceased. The data gained will be analysed as above using an intention-to-treat basis.

In light of easing of lockdown the HIIT trial will resume using a remote cohort design. All eligible participants will receive HIIT, no randomisation will take place. A cohort design will be employed due to the smaller number of SMI patients receiving inpatient treatment during the outbreak/ slow resumption of inpatient admissions, thus it is unlikely that there will be enough numbers to randomise patients. The study primary and secondary outcomes remain the same.

HIIT sessions will resume remotely. This data will be analysed separately to existing data gathered from the RCT. A pre-post analysis on an ITT basis and a subgroup of those with 64% adherence will take place. The research team will conduct HIIT sessions remotely via a projector screen but a member of the ward will supervise sessions in person. Adverse events/ injuries/ difficulties will be observed by both the researcher remotely and the in-person staff member. Baseline and follow-up assessments will be conducted remotely via a projector screen/ telephone call for questionnaire measures.

A target of 6-8 patients will be recruited to the cohort study design.

Stage Three:

1. Qualitative interviews:

   Participants who completed the pilot study will be invited to take part in individual semi-structured follow-up qualitative interviews. Feedback regarding the acceptability and feasibility of the study will be sought. Additionally, feedback will be sought from those that withdrew from the study and those that did not agree to take part. The interviews will assess 1) how participants experienced the intervention, 2) if there are any parts of the intervention that could be improved, and what factors influenced people in completing/not completing the intervention. Interviews will take place on a one-to-one basis with a member of the research team and a participant. Each qualitative interview will be conducted within 3 weeks of each participant finishing the HIIT pilot study/ within 3 weeks of drop-out if time commitments permit. Responses will be recorded when permission has been granted. Overall, each individual interview will take 30- 60 minutes and will not require participants to participate in any follow-up tasks. The qualitative data gained from these questions will be analysed using thematic analysis to understand the main themes.
2. Focus groups:

Up to two focus groups with clinical staff at SLaM will be conducted and feedback regarding the acceptability and feasibility of the pilot HIIT study conducted in stage two of the research project will be sought. It is expected that between 6-8 people will attend each focus group. A series of simple open-ended questions will be asked, and participants will answer verbally. The questions will address staff's opinions regarding the acceptability and feasibility of conducting HIIT in a mental health setting. An audio-recording will record responses to these questions when permission has been granted. The qualitative data gained from these questions will be analysed using thematic analysis to understand the main themes. Overall, each focus group should take no more than 2 hours and will not require participants to participate in any follow-up tasks.

Eligibility criteria: Inclusion Criteria:

Stage 1 (Focus Groups):

* Capacity to provide informed consent.
* Aged ≥18 years.
* Either be: 1) Inpatients at SLaM with a diagnosis of SMI (Major Depressive Disorder, Bipolar disorder, Schizophrenia Spectrum Disorders, 2) Carers providing unpaid support to someone with a SMI, 3) Clinical staff at SLaM.

Stage 2 (HIIT Pilot RCT):

* Inpatients at SLaM with a diagnosis of SMI.
* Capacity to provide informed consent.
* Aged 18 -60.
* Ready to exercise according to the Physical Activity Readiness Questionnaire.

Stage 3 (Follow-up): Qualitative interview:

* inpatients who were eligible for stage 2.

Stage 3 (Follow-up): Focus group:

* staff who participated in stage 1.

Exclusion Criteria:

Stage 1 (Focus Groups):

* Is aged \<18 years old.

Stage 2 (HIIT Pilot RCT) \& Stage 3 qualitative interviews:

* Is aged \<18 years old or \>60 years old.
* Is pregnant.
* Has an eating disorder.
* Has a medical condition that impedes exercise, (as assessed via discussion with the patient's clinical team).

Stage 3 focus group:

* Did not complete stage one.

ALL STAGES:

* Is unable to provide informed consent.
* Is unable to understand English.

Primary outcomes:
measure: Number of wards that agree to hosting the HIIT Pilot Study and number that do not agree to hosting the HIIT pilot study
timeFrame: Through study completion, an average of 1 year
measure: Number of people who consent to take part
timeFrame: Through study completion, an average of 1 year
measure: Average adherence to HIIT sessions and assessments
timeFrame: Throughout length of participation in the HIIT trial, 12 weeks
measure: Number of Participants With Treatment-Related Adverse Events
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: BMI
timeFrame: baseline, 6-weeks, 12-weeks
measure: Weight
timeFrame: baseline, 6-weeks, 12-weeks
measure: Waist Circumference (WC)
timeFrame: baseline, 6-weeks, 12-weeks
measure: Systolic and diastolic blood pressure
timeFrame: baseline, 6-weeks, 12-weeks
measure: Maximal oxygen uptake (VO2max)
timeFrame: baseline, 6-weeks, 12-weeks
measure: Gait speed
timeFrame: baseline, 6-weeks, 12-weeks
measure: Change in Montreal Cognitive Assessment (MoCA) score
timeFrame: baseline, 6-weeks, 12-weeks
measure: Change in global assessment of functioning scale (GAF) score
timeFrame: baseline, 6-weeks, 12-weeks
measure: Change in Brief Psychiatric Rating Scale (BPRS) score
timeFrame: baseline, 6-weeks, 12-weeks
measure: Change in the brief insomnia severity index (ISI)
timeFrame: baseline, 6-weeks, 12-weeks
measure: Cigarette intake
timeFrame: baseline, 6-weeks, 12-weeks
measure: Change in Depression Anxiety Stress Scale short version (DASS21) score
timeFrame: baseline, before and after the first HIIT session (or before and after 19 minutes of rest for the TAU arm), 6-weeks, 12-weeks
measure: Change in the Rosenberg Self-Esteem Scale (RSES) score
timeFrame: baseline, 6-weeks, 12-weeks
measure: Change in the International Physical Activity Questionnaire (IPAQ) score
timeFrame: baseline, 6-weeks, 12-weeks
measure: Change in the Behavioural Regulation in Exercise Questionnaire-3 (BREQ-3) score
timeFrame: baseline, 6-weeks, 12-weeks
measure: Change in the Short Warwick Edinburgh Mental Well-being Scale (WEMWBS) score
timeFrame: baseline, 6-weeks, 12-weeks
Other outcomes:
measure: Appetite cravings
timeFrame: before and after the first HIIT session (or before and after 19 minutes of rest for the TAU arm
measure: Cigarette cravings
timeFrame: before and after the first HIIT session (or before and after 19 minutes of rest for the TAU arm
measure: Change in Subjective Exercise Experiences Scale (SEES) score
timeFrame: before and after the first HIIT session (or before and after 19 minutes of rest for the TAU arm
Locations:
city: London
country: United Kingdom
facility: Bethlem Royal Hospital, South London and maudsley NHS Trust
city: London
country: United Kingdom
facility: Maudsley Hospital, South London and Maudsley NHS Trust
Study officials:
affiliation: King's College London
name: Brendon Stubbs
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leon AC, Davis LL, Kraemer HC. The role and interpretation of pilot studies in clinical research. J Psychiatr Res. 2011 May;45(5):626-9. doi: 10.1016/j.jpsychires.2010.10.008. Epub 2010 Oct 28.
citation: DE Hert M, Correll CU, Bobes J, Cetkovich-Bakmas M, Cohen D, Asai I, Detraux J, Gautam S, Moller HJ, Ndetei DM, Newcomer JW, Uwakwe R, Leucht S. Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care. World Psychiatry. 2011 Feb;10(1):52-77. doi: 10.1002/j.2051-5545.2011.tb00014.x.
citation: De Hert M, Dekker JM, Wood D, Kahl KG, Holt RI, Moller HJ. Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC). Eur Psychiatry. 2009 Sep;24(6):412-24. doi: 10.1016/j.eurpsy.2009.01.005. Epub 2009 Aug 13.
citation: Hennekens CH, Hennekens AR, Hollar D, Casey DE. Schizophrenia and increased risks of cardiovascular disease. Am Heart J. 2005 Dec;150(6):1115-21. doi: 10.1016/j.ahj.2005.02.007.
citation: Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, Haukka J. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet. 2009 Aug 22;374(9690):620-7. doi: 10.1016/S0140-6736(09)60742-X.
citation: Weston KS, Wisloff U, Coombes JS. High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis. Br J Sports Med. 2014 Aug;48(16):1227-34. doi: 10.1136/bjsports-2013-092576. Epub 2013 Oct 21.
citation: Martland R, Onwumere J, Stubbs B, Gaughran F. Study protocol for a pilot high-intensity interval training intervention in inpatient mental health settings: a two-part study using a randomised controlled trial and naturalistic study design. Pilot Feasibility Stud. 2021 Nov 8;7(1):198. doi: 10.1186/s40814-021-00937-6.