Cognitive Impairment, Depressive Symptoms, Quality of Life
Conditions
Keywords
Depression, Cognitive functions, Quality of Life, Cancer, Virtual reality, Repetitive Transcranial Magnetic Stimulation
Brief summary
Despite its significant impact on individuals and healthcare systems, substantial gaps remain in the clinical and rehabilitative management of depression in oncology patients. Depression in cancer patients is often under-recognized and untreated, and screening tools and structured healthcare pathways are lacking. Even when depression is identified in oncology patients, evidence of effective treatments is limited. There are no specific guidelines for psychotropic drug use in cancer patients, and antidepressant efficacy is uncertain despite their frequent use. Emerging strategies like transcranial magnetic stimulation and cognitive rehabilitation show promising findings. However, the cost-effectiveness of therapeutic strategies is understudied. Repetitive transcranial magnetic stimulation (rTMS) is already used for the treatment and relapse prevention of depression both as monotherapy and as an add-on to antidepressant pharmacotherapy, and it appears effective in improving cognitive performance. However, it has not yet been applied to treat depressive disorders in oncology patients. Virtual reality-based cognitive behavioral intervention (VR-COG) is designed to improve cognitive functioning, a central feature of depression in oncological conditions. VR-COG enhances learning and skill acquisition with better ecological efficiency than traditional cognitive remediation programs. VR approaches are well-received by oncology patients and show promise in reducing anxiety and depressive symptoms. The trial aims to evaluate the effectiveness of highly specialized, nonpharmacological interventions on depressive symptoms and quality of life in oncology patients. Specifically, repetitive Transcranial Magnetic Stimulation (rTMS) and Virtual Reality-based Cognitive Remediation (VR-COG) will be analyzed, alongside standard Treatment as Usual (TAU), in comparison to TAU alone. This trial also aims at evaluate cognitive functioning, depression-related conditions and the cost-effectiveness of the interventions under study.
Interventions
DEVICEVirtual Reality-based Cognitive Remediation (VR-COG) + Treatment as Usual (TAU)
The CEREBRUM-VELA virtual reality software is made up of exercises designed to train different cognitive functions (i.e.: executive functions, motor ability, language). The different degrees of difficulty are designed to adapt to the user's functional diagnosis. Each session, after an initial part of welcome, psychoeducation and orientation to the instrument, involves alternating virtual reality exercises, positive and corrective feedback and suggestions of practical homework that the individual should try to do during his day. Treatment as usual (TAU) The path, following the guidelines of the Italian Association of Medical Oncology (AIOM-SIPO: https:// www.aiom.it), includes an initial psychiatric visit aimed at assessing the presence of psychopathological conditions that may necessitate pharmacological therapy (antidepressants, hypnotic-sedatives) and subsequent psychiatric follow-up. The treatment also involves psychological counseling (monthly sessions).
DEVICERepetitive transcranial magnetic stimulation (rTMS) + Treatment as usual (TAU)
Active rTMS stimulation will be delivered at 90% of the resting Motor Threshold (rMT), adjusted for the depth of the fcMRI-identified target. Personalized targets created for each individual will be located at various cortical depths. For safety reasons, the stimulation intensity will never exceed 120% of the rTMS. Treatment as usual (TAU) The path, following the guidelines of the Italian Association of Medical Oncology (AIOM-SIPO: https:// www.aiom.it), includes an initial psychiatric visit aimed at assessing the presence of psychopathological conditions that may necessitate pharmacological therapy (antidepressants, hypnotic-sedatives) and subsequent psychiatric follow-up. The treatment also involves psychological counseling (monthly sessions).
OTHERTreatment as Usual (TAU)
Treatment as usual (TAU) The path, following the guidelines of the Italian Association of Medical Oncology (AIOM-SIPO: https:// www.aiom.it), includes an initial psychiatric visit aimed at assessing the presence of psychopathological conditions that may necessitate pharmacological therapy (antidepressants, hypnotic-sedatives) and subsequent psychiatric follow-up. The treatment also involves psychological counseling (monthly sessions).
Sponsors
University Hospital of Cagliari
University Hospital of Ferrara
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of oncological disease in the last 5 years * Diagnosis of Major Depressive Disorder, without psychotic symptoms, according to DSM-5 criteria * 17-item Hamilton Rating Scale for Depression (HAM-D-17) (score ≥14) * Age: 18 years or older * Oncological disease in a non-advanced stage (Karnofsky Performance Status \> 80)
Exclusion criteria
* Current or prior hospitalization in the next 6 months * Planned surgery in the next 6 months * Suicidal ideation * Substance use * History of significant head trauma, neurological disorders, intellectual deficits * Recurrent seizures resulting from head trauma or conditions lowering seizure threshold * Concurrent use of medications that increase the risk of epileptic seizures (e.g., antipsychotics, tricyclics, theophylline) * Glaucoma, retinal detachment, or other serious vision impairments that may prevent the use of virtual reality technology * Severe problems with autonomous ambulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TMSens_Q | T0 (0 months - baseline); T1 (3 months - post intervention) | It was developed to report secondary effects following rTMS application. The use of the structured rTMS questionnaire will help to monitor the safety of rTMS. |
| Hamilton Depression rating scale (HAM-D 17) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | The Ham-D is the most widely used clinician-administered depression assessment scale.The original version contains 17 items pertaining to symptoms of depression experienced over the past week. |
| Dropout rates; Proportion of recruited participants among those considered eligible | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | Feasibility will be assessed based on tolerability (dropout rates) and acceptability (proportion of recruited participants among those considered eligible). |
| Simulator Sickness Questionnaire (SSQ) | T0 (0 months - baseline); T1 (3 months - post intervention) | Feasibility will be assessed based on side effects through Simulator Sickness Questionnaire (SSQ) self-report questionnaire that evaluates the frequency of unwanted effects due to virtual reality technologies, such as nausea, dizziness, headaches, eye strain, etc. 16 items. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SF-12 | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | It is a self-report questionnaire to assess quality of life considering two dimensions, about physical health and mental health. |
| Demoralization Scale (DS) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | It is a 24-item self-administered questionnaire with four subscales: discouragement, loss of meaning/purpose, dysphoria, sense of failure. |
| Post-Traumatic Embitterment Disorder Self-Rating Scale | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | It is a rating scale to assess embitterment reactions to negative life events |
| Biological Rhythms Interview for Assessment in Neuropsychiatry (BRIAN) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | It is a scale consisting of 18 items to assess four areas of circadian rhythm difficulties: sleep, activity, social rhythms, and eating patterns. |
| Activities of Daily Living (ADL) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | It is an instrument to assess disability levels. |
| Psychosocial Adjustment to Illness (PAIS) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | I is a self-report instrument to assess seven dimensions about disability and quality of life. |
| Toronto Alexithymia Scale 20-item (TAS-20) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | It is a self-report questionnaire to assess alexithymia. |
| Trail Making Test | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | Preliminary measures of effectiveness on executive function |
| Digit Span | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | Preliminary measures of effectiveness on memory |
| Stroop Test | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | Preliminary measures of effectiveness on executive function |
| Frontal Assessment Battery (FAB) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | Preliminary measures of effectiveness on executive function |
| Rey's Word Test | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | Preliminary measures of effectiveness on memory |
| Matrix test | T0 (0 months-baseline), T1 (3 months - post intervention), T2 (3 months after T1), T3 (6 months after T1) | Preliminary measure of effectiveness on selective attention. |
| Screen for Cognitive Impairment in Psychiatry (SCIP) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | It is an instrument to assess cognitive deficit according to five subscales: immediate memory, working memory, phonemic verbal fluency, delayed memory, and psychomotor speed. |
| Brief Symptom Inventory (BSI) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | Il is a questionnaire to evaluate symptoms of psychological distress |
| Insomnia Severity Index (ISI) | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | It is a tool to assess the severity of daytime and nighttime components of insomnia. |
| EuroQol (EQ)-5D | T0 (0 months - baseline); T1 (3 months - post intervention); T2 (3 months after T1); T3 (6 months after T1) | It is self-report questionnaire to assess quality of life and heath status according to five dimensions. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cost-effectiveness | T0 (0 months - baseline); T3 (6 months after T1-post intervention) | The cost effectiveness will be computed as the ratio of total costs divided by the mean improvements of quality of life across interventions (TAU, TAU+rTMS, TAU+VRCOG). Total costs will include the costs of the healthcare consultations (visits in the TAU condition), psychotropic drugs, equipment and staff. Total costs will be computed as the sum of these costs of each intervention, divided by the number of patients. Quality of life improvements will be computed as the difference between baseline (T0) vs endpoint (T3) quality of life. |
Countries
Italy
Contacts
Primary ContactMartino Belvederi Murri, MD
Backup ContactBarbara Zaccagnino, PsyD
Outcome results
None listed