Anxiety, Cancer in Remission (Any Type or Stage), Depression
Conditions
Keywords
repetitive Transcranial Magnetic Stimulation, Cancer Survivors, Depression, Anxiety
Brief summary
Cancer is a leading cause of mortality and morbidity worldwide. In addition, cancer is associated with high rates of depression and anxiety among its sufferers, and cancer patients with depression usually have worse treatment outcomes and long-term survival. Surprisingly, many cancer patients with depression do not receive treatment for their depression, perhaps because treatments for cancer-related depression are usually adapted from those used in non-cancer populations and may not be suitable for cancer patients. Moreover, cancer patients with depression are more likely to have a long latency of anti-depressant drug action, negative drug-drug interactions with cancer chemotherapies and an increased susceptibility for systemic side effects. Repetitive transcranial magnetic stimulation (rTMS) is a new treatment modality for depression that affects the brain directly with no systemic side effects and poses no potential for drug-drug interactions. rTMS therapy was recently cleared by the FDA as an antidepressant treatment for treatment-resistant Major Depressive Disorder, and now is being evaluated for a wide array of additional psychiatric indications. This randomized, open label, two-arm, pilot study will investigate the safety, tolerability, feasibility and the efficacy of two forms of rTMS (i.e., left (fast) and right (slow) sided rTMS) in cancer-related depression. The study hypotheses are that rTMS will significantly reduce symptoms of depression and that right-sided slow rTMS will be more effective than left-sided fast rTMS for the treatment of severe anxiety.
Interventions
DEVICERepetitive Transcranial Magnetic Stimulation (rTMS)
Sponsors
Northwestern University
Neuronetics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1\. Adults aged 22-80; 2. Have a previous diagnosis of cancer (any type or stage) as confirmed by official medical records; 3. Have a Diagnostic and Statistical Manual (DSM-IV) diagnosis of Major Depressive Disorder; 4. Have a Hamilton Depression Rating (HAM-D) 24-item score of more than 20; 5. Failed to receive satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current depressive episode; 6. All participants must have given signed, informed consent prior to registration in study.
Exclusion criteria
1\. Participant with any type of brain tumor; 2. Participant with cancer with brain metastases; 3. Evidence of the disease at the time of entry into the trial; 4. Presence or recent history of other concurrent cancers, with the following exceptions: a. Participants with completely treated basal or squamous skin cancers could be included in the study if their physicians deem that they are medically stable, b. Participants with completely treated in situ carcinoma of the breast or cervix could be included in the study if they have not had chemotherapy within the past month and their physicians deem that they are medically stable, c. Participants with pre-cancerous lesions in the colon could be included in the study if they have not had chemotherapy within the past month and their physicians deem that they are medically stable; 5. Participant had recent surgery within two weeks of screening; 6. Participants undergoing chemotherapy; 7. Participant pregnant or nursing; 8. Participant with any metallic object in or around their head; 9. Participant with a pacemaker; 10. Participants with unstable suicidal ideation as determined by the patient's treating psychiatrist; 11. Participants with a substance use disorder within the prior six months; 12. Significant history of head injury/trauma as defined by loss of consciousness for more than one hour; 13. Recurring seizures resulting from the head injury; 14. Clear cognitive sequelae from the head injury and cognitive rehabilitation following the injury; 15. Any disorder that would predispose the participant to seizures; 16. Use of concomitant medications that substantially increase seizure risk.; Such drugs could include neuroleptics (ex. haloperidol, droperidol), clozapine, tricyclic antidepressants (ex. amoxapine, clomipramine), bupropion (particularly the immediate release (IR) formulation), donepezil, psychostimulants (ex. methylphenidate), theophylline and/or other drugs that reduce the seizure threshold. For individuals on any of these medicines, a study clinician evaluated the drugs and doses to determine the risks and benefits. These were then discussed with the individual's Primary Care Physician to determine if the individual could be included in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Change in Depression Severity (HDRS-17) at Weeks 2, 4, and 6 | Baseline (Week 0), Week 2, Week 4 and Week 6. | This measure reports the overall change in depression severity(HDRS-17) from baseline (Week 0) at each follow-up assessment. Overall Change is defined as the score at each subsequent time point minus the score at Baseline. Scale Information: Name: Hamilton Depression Rating Scale (HDRS-17). Construct: The HDRS-17 is a clinician-administered assessment of depressive symptom severity. Total Score Calculation: The total score is calculated by summing the individual scores of all 17 items. Range: Total scores range from 0 to 52. Directionality: Higher values represent a worse outcome (more severe depression), while lower values represent a better outcome. Calculation Logic: The values reported are the absolute difference of outcomes for each treatment arm. For each participant, the relative change is calculated as: Score at Visit - Baseline Score. Negative numbers indicates a reduction in symptom severity (improvement) and a positive number indicates worsening in symptom severity |
| Relative Change in Depression Severity (HDRS-17) at Weeks 2, 4, and 6 | Baseline (Week 0), Week 2, Week 4 and Week 6 | Measure Description: This measure reports the relative (percentage) change in depression severity from baseline (Week 0) at each follow-up assessment. Scale Information: Name: Hamilton Depression Rating Scale (HDRS-17). Construct: The HDRS-17 is a clinician-administered assessment of depressive symptom severity. Total Score Calculation: The total score is calculated by summing the individual scores of all 17 items. Range: Total scores range from 0 to 52. Directionality: Higher values represent a worse outcome (more severe depression), while lower values represent a better outcome. Calculation Logic: The values reported are the mean percentage changes for each treatment arm. For each participant, the relative change is calculated as: ((Score at Visit - Baseline Score) / Baseline Score) \* 100. A negative percentage indicates a reduction in symptom severity (improvement). |
| Number of Participants With Treatment-Emergent Side Effects (UKU) | Baseline (Week 0), Week 2, Week 4, and Week 6 | Side effects assessed at Weeks 2, 4, 6 via Udvalg for Kliniske Undersøgelser (UKU) scale (48 items, 0=none to 3=severe; higher=worse). 'Treatment-emergent' worsening is a score increase ≥1 from baseline (Tx #1) on any item with possible/probable relation to intervention. Data reported is the count of participants meeting criteria for any of the clusters. Psychic Cluster: concentration, asthenia, sedation, memory, depression, unrest, sleep/dream changes, emotional indifference. Neurological Cluster: dystonia, rigidity, hypokinesia, hyperkinesia, tremor, akathisia, seizures, paresthesia, headache. Autonomic Cluster: accommodation, salivation, nausea/vomiting, diarrhea, constipation, micturition, polyuria, dizziness, tachycardia, sweating. Other Cluster: rash, pruritus, photosensitivity, weight change, menses changes, galactorrhea, gynecomastia, libido changes, erectile dysfunction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Change in Anxiety Severity (HAM-A) at Weeks 1, 2, 3, 4, 5, and 6 | Baseline (Week 0), Week 1- Week 6 (Weekly assessments) | Measure Description: The overall change in anxiety severity is assessed using the total score of the Hamilton Anxiety Rating Scale (HAM-A) at each protocol-specified follow-up visit compared to the baseline score at baseline(Week 0) Scale Information: Hamilton Anxiety Rating Scale (HAM-A) Construct: A clinician-rated scale used to measure the severity of a patient's anxiety symptoms, including both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints). Total Score Calculation: The total score is calculated by summing the individual scores of all 14 items. Range: Total scores range from 0 to 56. Directionality: Higher values represent a worse outcome (greater anxiety severity), while lower values represent a better outcome. Calculation Logic: The values reported represent the absolute difference in scores for each treatment arm at every assessment interval minus the score at baseline. |
| Relative Change in Anxiety Severity (HAM-A) at Weeks 1, 2, 3, 4, 5, and 6 | Baseline(Week 0), Week 1- Week 6 (Weekly assessments) | This measure reports the relative (percentage) change in anxiety severity from baseline (Week 0) at each follow-up assessment. Scale name: Hamilton Anxiety Rating Scale (HAM-A). It is a clinician-rated scale used to measure the severity of a patient's anxiety symptoms. The scale consists of 14 items, each defined by a series of symptoms, measuring both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe). Total score is calculated by summing all 14 items. The total Score ranges from 0 to 56. Higher values represent a worse outcome (greater severity of anxiety), while lower values represent a better outcome. For each protocol-specified time point (Weeks 1-6), the relative change is calculated for as: ((Score at Visit - Baseline Score(Week 0) /Baseline Score)\*100. A negative percentage indicates a reduction in symptoms (better outcome). |
| Correlation Between Baseline Anxiety (HAM-A) and Change in Depression Severity (HDRS-17, HAM-D) | Baseline (Week 0) and Week 6 | This measure assesses the relationship between the severity of anxiety symptoms at the start of treatment and the magnitude of depression improvement at Week 6. Scale 1: Hamilton Anxiety Rating Scale (HAM-A). Measures anxiety severity. Total range: 0 to 56. Higher values = worse outcome. Scale 2: Hamilton Depression Rating Scale (HDRS-17, HAM-D). Measures depression severity. Total range: 0 to 50. Higher values = worse outcome. Statistical Analysis \& Interpretation: Change Calculation: Depression change is calculated as (Week 6 Score - Baseline Score). A more negative value represents greater improvement. Coefficient: Spearman's rank correlation coefficient (rho) is used. Interpretation: A positive correlation indicates that higher baseline anxiety is associated with higher (less negative) change scores, meaning less improvement. A negative correlation indicates that higher baseline anxiety is associated with lower (more negative) change scores, meaning greater improvement. |
| Correlation Between Baseline Anxiety (HAM-A) and Harm Avoidance (TCI-R) | Baseline | This measure assesses the relationship between clinical anxiety symptoms and the personality trait of Harm Avoidance at baseline. Scale Information: Scale 1: Hamilton Anxiety Rating Scale (HAM-A). Measures anxiety severity. Total range: 0 to 56. Higher values = worse outcome. Scale 2: Temperament and Character Inventory-Revised (TCI-R) - Harm Avoidance Subscale. Measures the personality trait of Harm Avoidance. Results are reported as standardized T-scores (mean of 50, standard deviation of 10). The typical range for T-scores is 20 to 80. Outcome Direction: For both scales, higher values represent higher levels of the construct (more anxiety and higher harm avoidance). Statistical Analysis \& Interpretation: Coefficient: Spearman's rank correlation coefficient (rho). Interpretation: A positive correlation indicates that individuals with higher clinical anxiety symptoms also tend to score higher on the personality trait of Harm Avoidance. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMehmet Dokucu, MD, PhD
Northwestern University
Participant flow
Pre-assignment details
In the right-sided 1Hz frequency arm 1 participant withdrew consent after randomization but before treatment start. In the left-sided 10 Hz frequency arm 1 participant withdrew consent after randomization but before treatment start, another 1 participant withdrew consent after randomization and after a single treatment session but unrelated to any adverse events and 1 participant treatment was ended due to an adverse event determined to be NOT related to treatment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Age | 60.55 years STANDARD_DEVIATION 10.24 |
| Hamilton Depression Rating Scale (Also known as HAM-D or HDRS) | 26.17 units on a scale STANDARD_DEVIATION 2.41 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 2 Participants |
| The Hamilton Anxiety Rating Scale (HAM-A) | 21.38 units on a scale STANDARD_DEVIATION 5.97 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 8 |
| other Total, other adverse events | 12 / 12 | 8 / 8 |
| serious Total, serious adverse events | 0 / 12 | 0 / 8 |
Outcome results
None listed