Depression Clinical Trial
Effectiveness of a Brief Manualized Intervention Managing Cancer and Living Meaningfully (CALM) Adapted to the Italian Cancer Care Setting. Study Protocol for a Randomized Controlled Trial
Background: Patients with advanced cancer suffer from a variety of psycho-social symptoms
that impair quality of life and may benefit from psychotherapeutic treatment. We describe
here the methodology of a randomized controlled trial to test the effectiveness of a novel
and brief semi-structured psychotherapeutic intervention, called Managing Cancer and Living
Meaningfully (CALM), originally developed in Canada and now cross-culturally tested in Italy.
Methods/Design: The study is a single-blinded randomized controlled trial with 2 conditions: CALM intervention versus nonspecific supportive intervention (SPI) and assessments at baseline, 3 and 6 months. The coordinating site is the Program on Psycho-Oncology and Psychiatry in Palliative Care, University of Ferrara and Integrated Department of Mental Health, S. Anna University Hospital, in Ferrara, Italy. Other centres from northern and southern Italy will collaborate. Eligibility criteria include: ≥ 18 years of age; Italian fluency; no cognitive impairment; and diagnosis of advanced cancer. The intervention consists of 12 sessions , following the CALM manual and allowing for flexibility to meet individual patients' needs. It is delivered over a 6-month period and provides reflective space for patients (and their primary caregivers) to address 4 main domains: symptom management and communication with health care providers; changes in self and relations with close others; sense of meaning and purpose; and the future and mortality. The primary outcome is depression and the primary endpoint is at 6 months. Secondary outcomes include demoralization, generalized anxiety, death anxiety, spiritual well-being, quality of life, attachment security, posttraumatic growth, communication with partners, and satisfaction with clinical interactions.
Discussion: This trial is being conducted to determine the effectiveness of CALM in an Italian cancer setting. The intervention has potential cross-national relevance and, if shown to be effective, has the potential to be disseminated as a new approach in oncology to relieve distress and promote psychological well-being in patients with advanced cancer.
The study is coordinated by the Program on Psycho-Oncology and Palliative Care, Institute of
Psychiatry, University of Ferrara and University Hospital Psychiatry Unit, Integrated
Department of Mental Health, S. Anna University Hospital and Health Authorities in Ferrara,
Northern Italy. Other centres from northern and southern Italy will collaborate. The authors
R.C. and L.G. were directly trained in CALM in the Department of Supportive Care, Princess
Margaret Cancer Center, Toronto. Other trained professionals in psychotherapy and
psycho-oncology will also provide CALM interventions, after having attended a training course
carried out by the principal investigators (RC, LG). The study is designed as a
single-blinded randomized-controlled trial with two arms, experimental group and control
group. Participants in the experimental group will receive the CALM intervention for advanced
cancer, while those in Control Group will receive a supportive intervention (SPI) , which is
usual psycho-oncology care in our settings.
The primary outcome is the improvement of depression. The primary endpoint is 6 months. Secondary outcomes include demoralization, generalized anxiety, death anxiety, spiritual well-being, quality of life, attachment security, posttraumatic growth, communication with partners, and satisfaction with clinical interactions.
The study has been submitted for approval to the University Hospital and Health Authorities Ethical Committee of Ferrara, and to the Ethical Committees of the other collaborating centres in Turin, Florence and Cosenza, Italy.
Pilot phase - In line with the approach of the original authors and other international CALM investigators, a preliminary pilot un-blinded study was carried out over a one-year period in our centre, prior to initiating the CALM randomized controlled trial . This pilot phase had the aim of testing and assessing the feasibility of and the standard operating procedures outlined for the CALM randomized controlled trial, and the acceptability of the intervention within an Italian context. This was important since concepts of meaning, spirituality, existential growth and attachment might emerge differently in the Italian setting than in the Canadian setting where CALM was developed. The subjective experience of participants receiving this intervention was also examined qualitatively. Patient recruitment followed the procedure outlined for the CALM randomized controlled trial, except there was no blinding.
Patients in the experimental group will receive the brief, individual, manualized CALM intervention, a semi-structured psychotherapy designed for patients with advanced cancer. CALM was developed based on empirical results, clinical observation and the theoretical foundations of supportive-expressive and existential approaches, as well psychodynamic and attachment theories. In this Italian adaptation, CALM consists of 12 individual sessions (45-60 minutes each), instead of the original 6 sessions. The sessions are delivered bimonthly over a period of 6 months.
According to the original protocol and the CALM manual, the intervention covers four domains, namely: 1) Symptom management and communication with health care providers, aimed at improving cooperation and communication with health care providers, and consequently medical decision-making and control of symptoms; 2) Changes in self and relations with close others, aimed at supporting disruptions of self-esteem and identity related to cancer and its treatment. 3) Spiritual well-being, sense of meaning and purpose, aimed at addressing changes in life priorities and the meaning of the suffering related to the advanced phase of cancer; 4) Preparing for the future, sustaining hope and facing mortality, aimed at addressing existential fears and concerns, planning advanced treatment, and preparing for the process of dying.
All domains are addressed with each patient, but the time devoted to each module varies, based on the concerns that emerge as most relevant to each patient in specific sessions. The participant's principal caregiver is invited to participate in one or more of the sessions, as deemed appropriate by the therapist.
At any time during the intervention, patients deemed to be at acute risk for suicide, or who demonstrate significant worsening of depression, or who require treatment for other psychiatric co-morbidities, based on the clinical judgment of the therapists, are referred for psychiatric assessment and treatment.
Non-manualized supportive psycho-oncology intervention (SPI) The Control group intervention (SPI) includes counseling, information, crisis intervention, which is the usual care intervention provided in our center. As with CALM patients, SPI patients receive up to twelve sessions of individual therapy during a period of 6 months, each session lasting 50 minutes.
Inclusion and exclusion criteria
Eligible patients referred to receive psychosocial support from any of the collaborating departments are invited by a research assistant to take part in the study and signed informed consent will be obtained from consenting patients. Inclusion criteria are: 1) 18 years of age or more; 2) fluency in Italian language; 3) absence of cognitive deficit documented in the clinical records; 4) diagnosis of "wet" stage IIIB or IV lung cancer; any stage of pancreatic cancer, stage III or IV ovarian and fallopian tube cancers, or other stage IV gynecological cancer; and stage IV breast, genitourinary, gastrointestinal, melanoma, sarcoma, or endocrine cancers (all with an expected survival of 12-18 months); a score ≥10 at the Patient Health Questionnaire (PHQ9) and/or ≥ 20 at the Death and Dying Distress Scale (DADDS). Exclusion criteria are: 1) language barriers hindering psychotherapy; 2) inability to commit to the required 12 sessions; 3) concomitant psychotherapy.
Study participants are randomly assigned to receive either CALM or SPI. After obtaining informed consent by a patient, a research assistant includes his/her data on the random allocation list and informs the PI's about treatment allocation (CALM or SPI). The patient is not informed about their treatment condition (CaLM or SPI).
Quality standards and therapists training
The CALM Treatment Manual The research group translated and adapted the CALM Treatment Manual into the Italian language.
Therapist qualifications The investigators and therapists are psychiatrists and clinical psychologists trained in psychotherapy with psycho-oncology expertise.
CALM training CALM therapists receive a comprehensive CALM training at the study center. Therapists randomized to the control condition do not receive any additional training.
Supervision In order to ensure the quality of therapy and treatment fidelity, both CALM and SPI therapists receive regular supervision by experienced supervisors.
The Patient Health Questionnaire (PHQ-9) is a 9-item measure of depression. It is composed by nine items, reflecting DSM-IV criteria for major depression. A four-point Likert scale scores from 0 (not at all) to 3 (nearly every day), with a cut-off score of ≥10 suggesting depression. For study purposes, two additional items assessing self-harm intention and rating how difficult these symptoms have made it to do lead one's life, have been included.
The Demoralization Scale (DS) is a 24-item self-report tool assessing demoralization components of loss of meaning and purpose, dysphoria, disheartenment and helplessness. Items are scored on a five-point Likert scale ranging from 0 (never) to 4 (all the time). Low levels of demoralization were indicated by a score 10, moderate demoralization by a score 11-36, and high demoralization by a score > 37.
The Generalized Anxiety Disorder Questionnaire (GAD-7) is a 7-item self-report instrument screening the severity of GAD symptoms. Items are scored on a four-point Likert scale ranging from 0 (not at all) to 3 (nearly every day). Scores ≤4 indicate absence of anxiety, scores from 5 to 9 suggest that mild anxiety is present, and scores from 10 to 15 indicate moderate levels of anxiety. An eighth item rating how difficult these symptoms have made it to lead one's daily life has been included.
The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-SP)[v] is a 12-item self-report tool, exploring spiritual well-being, in terms of sense of meaning, faith and inner peace. Items are scored on a five-point Likert scale from 0 (not at all) to 4 (very much), with higher scores indicating a greater spiritual wellbeing.
The Posttraumatic Growth Inventory (PTGI) is a 21-item self-report measure of positive psychological changes after traumatic events. It consists of four subscales: New Possibilities, Appreciation of Life, Relating to Others and Spiritual Change. Items are scored on a three-point Likert scale ranging from 0 (not at all) to 2 (very much) with higher scores indicating greater post-traumatic growth.
The Quality of Life at the End of Life-Cancer Scale (QUAL-EC) is a self- report measure of quality of life in patients near the end of life. It originally consists of four subscales: Symptom Control, Relationship with Health Care Providers, Preparation for End of Life and Life Completion. For this study purposes, the symptom control subscale is not included, thus only items 4-17 are used. Items are scored on a five-point Likert scale ranging from 1 (not at all) to 5 (completely), with higher scores indicating higher quality of life.
The Death and Dying Distress Scale (DADDS), is a 15-item self-report measure assessing specific concerns of advanced cancer patients about end of life, feeling a burden to others and wasted opportunities. It is scored on a six-point Likert scale from 0 (no distress) to 5 (very much distress), with higher scores indicating higher death anxiety and distress.
The Experiences in Close Relationships Inventory Modified Short Form Version (ECR-M16), is used in its 16-item self-report form to measure the attachment style. The scale yields scores on two dimensions of attachment: avoidance and anxiety. Items are scored on a seven-point Likert scale ranging from 1 (disagree) to 7 (agree), with a total sum score on each subscale ranging from 16 to 56. Higher scores on both subscales indicate higher attachment insecurity.
The Memorial Symptom Assessment Scale (MSAS) [x]assesses the disease symptom severity. The scale, in its shortened version (MSAS- short form), measures the presence and severity of 28 common physical symptoms of cancer. Items are scored on a five-point Likert scale ranging from 0 (not at all) to 4 (very much).
The Couple Communication Scale (CCS) is used for participants who have a partner. The 10-item CCS taken from the PREPARE/ENRICH Inventory is concerned with an individual's feelings, beliefs, and attitudes about the communication in his/her romantic relationship. Each item is scored from 1 (strongly disagree) to 5 (strongly agree).
Intervention and control participants will complete the Clinical Evaluation Questionnaire (CEQ) at 3 and 6-months. The CEQ is a seven-item self-report questionnaire which assesses the amount of clinical benefit patients have experienced by from therapy at the time of the assessment. Items are rated from 0 to 4, with 0 (no clinical benefit) and 4 (a great clinical benefit).
Satisfaction of patients will also be qualitatively assessed by inviting them to share comments in a written form after completing CEQ questionnaire.
At baseline (T0), participants provide demographics and medical and treatment data using a standardized questionnaire and will complete all outcome measures, with the exception of the CEQ. The PHQ-9 and DADDS are first administered to assess eligibility prior to study entry, followed by the remaining baseline outcomes. Follow-up assessments on all outcomes are collected at three months (T1) and six months (T2). The CEQ is administered only at three months (T1) and six months (T2) as it is an evaluation of the intervention received to date. At T2, participants will also be queried about their having remained blind (or not) to randomization.
to detect an affect size (Cohens'd) of 0.45 with 80% power and alpha set to 0.05 with a correlation of 0.70 between baseline and endpoint assessment, a sample size of 41 individuals per group would be required at study end. Assuming a study completion rate of 80% and a treatment compliance rate of 90%, then 63 individuals per group would be required at baseline, or a total of 126 individuals at baseline.
Statistical analyses will be carried out by using the Statistical Package for Social Science Statistic program. For the final analyses we will use an intention-to- treat approach and compare patients in the assigned groups. Main analyses to evaluate effectiveness regarding primary and secondary outcomes will be performed using analysis of covariance (ANCOVA). We hypothesize that mean depression scores in the intervention group will be lower than in the control group at 3 and 6 months, when controlled for baseline and relevant disease-related covariates. As a sensitivity analysis, we will use multiple imputation to examine the influence of missing values. Lastly, prior trial results suggest that there may be group differences in the processing of death-related distress such that individuals with moderate death anxiety are more responsive to intervention than those with low death anxiety (approximately the lower third of the distribution) or high death anxiety (the upper third). We plan to conduct a subanalysis to confirm this effect.
Failure to sustain "double awareness" of engaging with life while facing one's imminent death is a risk in advanced phases of cancer and may be associated with depression, demoralization and other facets of existential distress, thus complicating adjustment at the end of life. CALM is a novel psychotherapeutic intervention aimed at reducing depression, anxiety and demoralization in advanced cancer patients, while promoting meaning-making processes. This trial is being conducted to determine the effectiveness of CALM in an Italian cancer setting. The intervention has possible cross-national relevance and, if shown to be effective, has the potential to be disseminated as a new approach in oncology to relieve distress and promote psychological well-being in patients with advanced cancer. ;
|Source||Università degli Studi di Ferrara|
|Contact||Luigi Grassi, M.D.|
|Phone||+39 0532 236409|
|Start date||October 11, 2018|
|Completion date||September 2019|
||Phase 2/Phase 3|
|Active, not recruiting||
|Active, not recruiting||
|Enrolling by invitation||
|Enrolling by invitation||
|Not yet recruiting||
|Not yet recruiting||
|Not yet recruiting||
||Early Phase 1|
|Not yet recruiting||
|Not yet recruiting||
|Not yet recruiting||