Repetitive Transcranial Magnetic Stimulation in Cancer Patients With Depression and Anxiety

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Open-Label Pilot Trial To Evaluate The Safety And Efficacy Of Repetitive Transcranial Magnetic Stimulation In Cancer Patients With Depression And Anxiety

Conditions
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Cancer in Remission (Any Type or Stage), Depression, Anxiety

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Age 22-80 Had a previous diagnosis of cancer (any type or stage) confirmed by official medical records Has a DSM IV diagnosis of Major Depressive Disorder Has a HAM-D 24-item score of more than 20 Failed to receive satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current depressive episode All participants must have given signed, informed consent prior to registration in study Exclusion Criteria: Participant had breast cancer with brain metastases There is evidence of the disease at the time of entry into the trial Presence or recent history of other concurrent cancers, with the following exceptions: Participants with completely treated basal or squamous skin cancers can be included in the study if their physicians deem that they are medically stable Participants with completely treated in situ carcinoma of the breast or cervix may be included in the study if they have not had chemotherapy within the past month and their physicians deem that they are medically stable Participants with pre-cancerous lesions in the colon can be included in the study if they have not had chemotherapy within the past month and their physicians deem that they are medically stable Participant had recent surgery (within two weeks) Participant is undergoing chemotherapy Participant is pregnant or nursing Participant has any metallic object in or around their head Participant has a pacemaker Has unstable suicidal ideation as determined by the patient's treating psychiatrist Substance use disorder within the prior six months Significant history of head injury/trauma as defined by loss of consciousness for more than 1 hour Recurring seizures resulting from the head injury Clear cognitive sequelae from the head injury and cognitive rehabilitation following the injury Any disorder that would predispose the participant to seizures 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 will evaluate the drugs and doses to determine the risks and benefits. These will then be discussed with the individual's Primary Care Physician to determine if the individual should be excluded from the study.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Right-Sided Low-Frequency rTMS<br>Participants will have rTMS administered at 1Hz to the right dorsolateral Prefrontal Cortex (dlPFC) once a day for 40 minutes, 5 days a week, for a total of six weeks. | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br> <br> * Other names: Neurostar TMS Therapy(R) System;|
| Experimental: Left-Sided High-Frequency rTMS<br>Participants will have rTMS administered at 10Hz to the left dorsolateral Prefrontal Cortex (dlPFC) once a day for 40 minutes, 5 days a week, for a total of six weeks. | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br> <br> * Other names: Neurostar TMS Therapy(R) System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall change in depression severity | Overall change in depression severity (as measured by the Hamilton Depression Rating Scale) will be measured for each treatment arm. | 0, 2, 4, and 6 weeks | 
| Relative change in depression severity | Change in depression severity (as measured by the Hamilton Depression Rating Scale) for a treatment arm will be compared relative to change in depression severity in the other treatment arm. | 0, 2, 4, and 6 weeks | 
| Presence and changes in severity of side effects | At weeks 2, 4 and 6, UKU Side Effects Rating Scale scores will be compared to baseline UKU scores to determine changes in presence and severity of side effects. Additionally, UKU scores at weeks 2, 4, and 6 will be used to determine probability that side effects are related to intervention. | 0, 2, 4, and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall change in anxiety severity | Overall change in anxiety severity (as measured by the Hamilton Anxiety Rating Scale) will be measured for each treatment arm. | Weekly (starting with week 0 through week 6) | 
| Relative change in anxiety severity | Change in anxiety severity (as measured by the Hamilton Anxiety Rating Scale) for a treatment arm will be compared relative to change in anxiety severity in the other treatment arm. | Weekly (starting with week 0 through week 6) | 
| Correlation of anxiety with change in depression severity | Baseline anxiety severity (as measured by the Hamilton Anxiety Rating Scale) will be correlated with change (from baseline to end of week 6) in depression severity (as measured by the Hamilton Depression Rating Scale) for each treatment arm and compared. | 0 and 6 weeks | 
| Correlation of anxiety with harm avoidance personality trait | Baseline anxiety severity (as measured by the Hamilton Anxiety Rating Scale) will be correlated with Harm Avoidance scores from the TCI personality inventory | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer Survivors, repetitive Transcranial Magnetic Stimulation, Depression, Anxiety