Impact of Group Psychological Interventions on Extracellular Vesicles in People Who Had Cancer

Study Overview
=================
Brief Summary
-----------------
Background: There is some evidence demonstrating the effect of psychological interventions in improvements in health biological parameters. To best of our knowledge, no study had addressed the impact of any psychological intervention on extracellular vesicles. In addition, Mindfulness-Based Cognitive Therapy (MBCT) and Emotion Focused Therapy for Cancer Recovery (EFT-CR) in the group have never been explored regarding extracellular vesicles and the effectiveness of these was not compared yet. Objectives: To explore and compare the effect of MBCT and EFT-CR on biological parameters and psychological variables in distressed people who have had breast, prostate and colorectal cancer; In addition, we will explore the acceptability through recruitment and retention rates of MBCT and EFT-CR in group and evaluate whether these interventions are appropriate for a larger clinical trial. Methods: The design of this study is a parallel randomized controlled trial. Participants will be randomized into MBCT, EFT-CR or usual care. Outcome measures will be assessed before, at the end of the intervention (8 weeks) and follow-ups (24 and 52 weeks from the baseline moment). Hypotheses: The researchers expected that both interventions will have an effect on extracellular vesicles and other study biomarkers as well as improvements in psychological outcomes, compared to treatment as usual (TAU) group. Regarding the comparative effectiveness, we did not have evidence to hypothesize which one of the interventions will be superior in both biological (extracellular vesicles) and psychological outcomes. Contribution for practice: The results of this preliminary study would permit to know if there are benefits of these psychological interventions on changes in extracellular vesicles and on psychological outcomes related to health. In addition, this study will permit to determine the acceptability of conducting a larger randomized controlled trial.

Official Title
-----------------
Impact of Mindfulness-Based Cognitive Therapy and Emotion Focused Therapy Group for Cancer Recovery Interventions on Extracellular Vesicles and Psychological Distress in People Who Had Breast, Colorectal or Prostate Cancer: A Preliminary Parallel Randomized Controlled Trial

Conditions
-----------------
Cancer

Intervention / Treatment
-----------------
* Behavioral: Mindfulness Based-Cognitive Therapy (MBCT)
* Behavioral: Emotion Focused Therapy Group for Cancer Recovery (EFT-CR)
* Other: Treatment as usual (no intervention)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women Aged 18 to 65 Diagnosed with breast, prostate, or colorectal cancer Have been diagnosed with cancer stage I-III Have finished cancer treatments from 3 months to 2 years (it will be included ongoing hormonal therapies) Experiencing significant distress (5 or more) on the Distress Thermometer at baseline Available to attend the intervention for the trial duration Sufficient functional ability to participate in intervention groups (ECOG) Ability to speak and write Portuguese and literacy to autonomous completion of questionnaires Exclusion Criteria: Patients in treatments such as ongoing chemotherapy or radiotherapy, or trastuzumab therapy Patients with ostomy A diagnosis of a concurrent disorder of psychosis, substance abuse, bipolar disorder, or active suicidality Current use of antipsychotics Current use of anti-inflammatory medication (corticotherapy) Currently engaging in a mindfulness meditation practice or yoga, or having done so within the previous year Being under any actual psychosocial or psychological treatment Participation in a MBCT program in the last five years Pregnancy or breast feeding A diagnosis of a concurrent autoimmune disorder Study Population Description: Participants will be recruited in the Portuguese Oncology Institute of Porto (Porto, Portugal), which is a reference public hospital in the north of the country offering cancer treatments.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mindfulness (MBCT)<br>Group therapy based on Mindfulness Based-Cognitive Therapy (MBCT). | Behavioral: Mindfulness Based-Cognitive Therapy (MBCT)<br>* MBCT is a program developed by Zindel Segal, Mark Williams and John Teasdale. During MBCT patients learn to decenter their negative thoughts and feelings, allowing the mind to move from an automatic thought pattern to conscious emotional processing. Mindfulness practices included in this program are breath awareness, body scan, sitting and walking meditation, and mindful yoga. The intervention will have the following structure: 8 weekly face-to-face meetings of 2 hours in a group format, daily home-based practice of learned skills, 4 hours of retreat/intensive group work after the fifth week, 6 months of home practice, 4 monthly consolidation face-to-face sessions.<br>|
| Experimental: Emotion Focused Therapy (EFT-CR)<br>Group therapy based on Emotion Focused Therapy for Cancer Recovery (EFT-CR). | Behavioral: Emotion Focused Therapy Group for Cancer Recovery (EFT-CR)<br>* EFT-CR is an evidence-based approach to psychotherapy, which combines aspects of person-centered, gestalt and existential therapies with contemporary emotion theory and dialectical constructivism (Elliott et al, 2004, Rice & Greenberg, 1984). On EFT-CR, therapist follows the client experience and guides the process, proposing therapeutic tasks when specific client behaviors occur. EFT-CR uses a set of emotion change principles which guide a process of emotional deepening process, from undifferentiated distress to secondary reactive emotions to primary maladaptive emotions to core pain and thence to primary adaptive emotions and emotional transformation (Elliott & Greenberg 2016). The intervention will have the following structure: 8 weekly face-to-face meetings of 2 hours in a group format, daily home-based practice of learned skills, 4 hours of retreat/intensive group work after the fifth week, 6 months of home practice, 4 monthly consolidation face-to-face sessions.<br>|
| Other: Control Group<br>Treatment as Usual is the condition in which participants will follow the usual institutional intervention protocol for medical follow-up and identification, referral and intervention for people identified with significant distress difficulties. | Other: Treatment as usual (no intervention)<br>* Treatment as Usual is the condition in which participants will follow the usual institutional intervention protocol for medical follow-up and identification, referral and intervention for people identified with significant distress difficulties.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change on Extracellular vesicles number by ultracentrifugation with sucrose cushion | The collected extracellular vesicles will be quantified by Nanoparticle tracking analysis (Nanosight Ltd.), and data will be measured in particles per milliliter (mL). NTA measures Brownian movements on a particle-by-particle basis tracking movements by image analysis. Additionally, miR21-5p - a brain related microRNA - will be measured to ascertain for the extracellular vesicle's origin. The latter will be achieved by isothermal DNA amplification method, and data will be measured by luminescence (in RLU - relative light unit). | T0-before intervention; T1-8 weeks after T0; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on anxiety, depression and stress (Depression Anxiety Stress Scales, DASS21) | This self-report instrument assess the depressive, anxiety and stress symptoms in a 4-points likert scale, from 0 to 3, with higher values representing higher depression, anxiety and stress symptoms | T0-before intervention; T1-8 weeks after T0; T2-24 weeks after T0; T3-52 weeks after T0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change on Cancer antigen (CA 15-3) | This indicator assess CA 15-3 (units/mL) using an immunoassay analyzer | T0-before intervention;T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on Prostate-specific antigen (PSA) | This indicator assess PSA (ng/mL) using an immunoassay analyzer | T0-before intervention;T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on Carcinoembryonic Antigen assays (CEA) | This indicator assess CEA (ng/mL) using an immunoassay analyzer | T0-before intervention;T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on Adrenocorticotropic Hormone (ACTH) | This indicator assess ACTH (pg/mL) using an immunoassay analyzer | T0-before intervention;T2-24 weeks after T0; T3-52 weeks after T0 | 
| Transcript inflammatory response genes (IL-1, IL-6, IL-8, IL-10, IFNγ and TNF) | These indicators assess inflammatory response genes in plasma by Quantitative RT-PCR assays of the same individuals using TaqMan™ Gene Expression Assays | T0-before intervention; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on Analytic biomarkers (Erythrocytes number) | This indicator assess erythrocytes number (million/mm3) from blood samples(Sysmex XN) | T0-before intervention; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on Analytic biomarkers (PCR number) | This indicator assess PCR (mg/L) from blood samples | T0-before intervention; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on Analytic biomarkers (telomerase activity) | This indicator assess telomerase activity (units) from blood samples | T0-before intervention; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on Analytic biomarkers (hemoglobin glycosylated (HPLC)) | This indicator assess HPLC (mmol/mol) from blood samples | T0-before intervention; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on Global distress (Clinical Outcome Routine Evaluation - Outcome Measure, CORE-OM) | This self-report measure assesses global distress in four domains: subjective well-being, symptoms, social/life functioning, risk to self and others, rated in 5-points likert scale from never to always. Higher scores meaning higher psychological suffering | T0-before intervention; T1-8 weeks after T0; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on quality of life (Functional Assessment of Cancer Therapy, FACT) | These self-report instrument assess perceived quality of life related to the cancer, in a 5-points likert scale, from 0 to 4, with higher value indicated higher quality of life | T0-before intervention; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on quality of life (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale, FACIT-SP) | These self-report instruments assess perceived spiritually related to the cancer in a 5-points likert scale, from 0 to 4, with higher value indicated higher well-being | T0-before intervention; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on fear of cancer recurrence (Fear of Cancer Recurrence, FCR-7) | This self-report instrument assess the fear of cancer recurrence, rated in a 5-points likert scale, with higher values indicated higher fear of recurrence | T0-before intervention; T1-8 weeks after T0; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on satisfaction perceived social support (ESSS) | This self-report instrument assess the perceived level of social support, rated in a 5-points likert scale, with higher values meaning higher social support | T0-before intervention; T1-8 weeks after T0; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on emotional regulation processes (Emotion Regulation Questionnaire, ERQ, emotion suppression subscale) | This self-report measure assess the emotion regulation processes rated in a 7-points likert scale, with higher values representing higher emotional suppression | T0-before intervention; T1-8 weeks after T0; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on impact of events (Impact of Event Scale - Revised, IES-R) | This self-report measure assess the impact of significant events, rated in a 5-points likert scale, with higher scores meaning higher negative impact of the event | T0-before intervention; T1-8 weeks after T0; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on Mindfulness Attention and Awareness (Mindfulness Attention and Awareness Scale, MAAS) | This self-report measure assess the mindfulness and awareness skills, rated in a 6-points likert scale with higher scores indicating higher attention and awareness | T0-before intervention; T1-8 weeks after T0; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on self-compassion skills (Self-Compassion Scale - Short Form, SHORT FORM) | This self-report measure assess the self-compassion skills, rated in 5-points likert scale, with higher scores indicating higher self-compassion | T0-before intervention; T1-8 weeks after T0; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change Interview (Elliot, 1999) | This interview assesses the psycho-therapeutic changes perceived by participants after psychological intervention. The interview questions explore the changes that a person has noticed since therapy began, what the person attributes these changes to, and helpful and unhelpful aspects of therapy, in a qualitative way. In addition, the participants identified therapeutic changes as result of the therapy and are asked to rate these changes in three scales: expected change (1: change totally expected; 5: totally unexpected); change without therapy (1: the change would not have happened; 5: change would happen for sure); and the value of the change (1: nothing important; 5: extremely important). | T2-24 weeks after T0 | 
| Change on smoking dependency (Fagestrom Test) | This instrument assesses nicotine dependency with 6 items (rated from 0 to 2 or 3). The total score range is 1-10, with higher values meaning higher nicotine dependency | T0-before intervention; T2-24 weeks after T0; T3-52 weeks after T0 | 
| Change on physical activity (IPAQ,The International Physical Activity Questionnaire) | This instrument assesses physical activity in 7 items, with higher scores meaning higher level of physical activity | T0-before intervention; T2-24 weeks after T0; T3-52 weeks after T0 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast cancer, Prostate cancer, Colorectal cancer, Psychological stress, Anxiety, Depression, Emotion Focused Therapy, Distress, Extracellular vesicles, Exosomes, Biomarkers, Inflammatory response genes, Group interventions, Mindfulness, Mindfulness Based Cognitive Therapy