治療困難なうつ病におけるRTMS治療のプライミング戦略としての運動の実現可能性試験
治療困難なうつ病におけるRTMS治療のプライミング戦略としての運動の実現可能性を評価するランダム化試験
The goal of this study is to collect feasibility data on combining structured exercise aimed to improve physical fitness, and intermittent TBS (iTBS) in treating individuals diagnosed with difficult-to-treat depression who are physically inactive. By conducting this trial, we will compare the therapeutic benefits of the combined approach against the standard treatment of iTBS alone (without exercise). These findings will be used to inform future large-scale projects in which we will investigate, in a larger sample size, whether structured exercise aimed to improve fitness as recommended by most public exercise guidelines (i.e., ≥3x/week, moderate-to-vigorous intensity) serves as an active ingredient that amplifies the effectiveness of iTBS. Ultimately, the insights gained from this study will be valuable for clinicians seeking to alleviate depressive symptoms in MDD through neuromodulation techniques such as iTBS.
調査の概要
詳細な説明
This is a randomized, two-arm, pilot feasibility clinical trial design involving physically inactive individuals diagnosed with treatment-resistant depression (TRD). Participants will be randomly assigned to either: 1) 4-weeks of exercise (moderate-to-vigorous intensity; ~1h session, 3x/week) followed by 6 weeks of iTBS combined with exercise (intervention group), or 2) 4 weeks of stable treatment (i.e. no change in psychotropic medication/psychotherapy regimen or physical activity) followed by 6 weeks of iTBS alone (control group). The intervention group is divided into two phases: the priming phase and the synergetic phase. Due to the neuroplasticity-enhancing effects of exercise and fitness, and based on pilot results demonstrating superior antidepressant effects of TBS in physically active participants, the main objective of the priming phase is to enhance brain plasticity mechanisms through increases in fitness from the 4 weeks of exercise training. In other words, this phase aims to build capacity for a better response to TBS treatment. The synergetic phase (interventional group) follows the priming and involves integrating TBS treatment into the exercise training regimen. Participants in the interventional group will maintain their exercise routine to enhance and sustain gains while undergoing TBS treatment for 6 weeks. In accordance with the recommended guidelines for both exercise and TBS treatment for depression, participants in the interventional group will engage in exercise sessions lasting approximately 1 hour, three times per week. In both interventional and control groups, TBS treatment will be administered five times per week, with treatment delivery lasting 3 minutes. We hypothesize that all aspects of this project will be feasible, that is the exercise and iTBS delivery and outcomes assessment. Additionally, we expect participants to show high levels of adherence and compliance with the strategy. The ultimate goal, to be investigated in a larger-scale study following this one, is to determine whether exercise acts as an active ingredient that enhances the effectiveness of iTBS.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Stacey Shim, MSc
- 電話番号：6356 613-722-6521
- メール：stacey.shim@theroyal.ca
研究連絡先のバックアップ
- 名前：Emma Cummings, BSc
- 電話番号：6586 6137226521
- メール：emma.cummings@theroyal.ca
研究場所
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Ontario
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Ottawa、Ontario、カナダ、k1z 7k4
- 募集
- Royal Ottawa Mental Health Centre
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コンタクト：
- Stacey Shim
- 電話番号：6137226521
- メール：stacey.shim@theroyal.ca
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Are between 18-75 years old.
- Able to provide voluntary informed consent.
- Diagnosis of MDD or Persistent Depressive Disorder, without psychotic features, confirmed by MINI for DSM-5.
- Depressive symptoms have not improved after ≥ 1 adequate antidepressant trial in the current episode (i.e., difficult-to-treat MDD), based on the Antidepressant Treatment History Form (ATHF).
- Baseline score of ≥15 on the HRSD-17.
- No change in psychotropic medications or psychotherapy regimen at least 4 weeks prior to entering the trial
- Physically inactive as per the International Physical Activity Questionnaire - Short Form (IPAQ-SF).
- Able to engage in structured exercise as per the Get Active Questionnaire (GAQ).
- Able to adhere to the proposed treatment schedule.
Exclusion Criteria:
- Diagnosis of bipolar I or II disorder, based on DSM-5 criteria.
- Current or past (<3 months) substance (excluding caffeine or nicotine) or alcohol abuse/dependence, as defined in DSM-5 criteria.
- Current use of illegal substances.
- Current use of cannabis.
- Concomitant major unstable medical or neurologic illness (e.g., uncontrolled diabetes or renal dysfunction).
- Organic cause of the depressive symptoms (e.g. thyroid dysfunctions), determined by the referring physician.
- Acute suicidality or threat to life from self-neglect.
- Pregnant or breastfeeding, or thinking of becoming pregnant during course of treatment.
- Contraindication for TMS and MRI (e.g., personal history of epilepsy or seizure, metallic head implant, pacemaker), confirmed by TMS Adult Safety Scale (TASS) and MRI pre-screener.
- Unwilling to maintain current psychotropic medication and/or psychotherapy regimen for the four weeks prior to and for the duration of the study.
- Taking more than 1 mg/day of lorazepam or equivalent.
- Any other condition that, in the opinion of the investigators which would adversely affect the participant's ability to complete the study.
- Physically active: performing exercise and/or physical activity levels meeting the cut-off for "minimally active" on the IPAQ-SF.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Intervention Group
4-weeks of exercise (moderate-to-vigorous intensity) followed by 6 weeks of iTBS combined with exercise. |
Cool B70 cooled-coil (left DLPFC) with X100 MagPro rTMS Device (Magventure A/S, Farum, Denmark)
他の名前：
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|
他の：Standard Group
Standard care of 4 weeks of stable treatment (i.e. no changes to antidepressant regimen or physical activity) followed by 6 weeks of iTBS alone. |
Cool B70 cooled-coil (left DLPFC) with X100 MagPro rTMS Device (Magventure A/S, Farum, Denmark)
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Assessing feasibility on combining structured exercise and intermittent Theta Burst Stimulation (iTBS) in participants with treatment-resistant depression (TRD)
時間枠：Assessed at the end of the study once all participants have completed the study.
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Feasibility outcomes are crucial metrics that will guide the refinement of our protocols, thereby enhancing our preparedness for future design endeavors. These will include: 1) recruitment, 2) adherence, 3) compliance, 4) retention, 5) satisfaction, and 6) adverse events. |
Assessed at the end of the study once all participants have completed the study.
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Compare the effects on clinical response of exercise on enhancing iTBS treatment efficacy vs. iTBS alone
時間枠：Administered at screening, before iTBS treatment course (week 4), at the end of the treatment course (week 10), then at the 6-week follow-up (week 16)
|
Clinical response will be defined as a ≥ 50% reduction in the 17-item Grid Hamilton Rating Scale for Depression (Grid-HRSD-17). The Grid HRSD is a clinician-rated instrument with seventeen items used to measure the severity of depressive episodes. The overall score ranges from 0 to 52, where scores of 0 to 7 are considered as being normal, 8 to 16 suggest mild depression, 17 to 23 moderate depression, and scores ≥ 24 indicate severe depression. |
Administered at screening, before iTBS treatment course (week 4), at the end of the treatment course (week 10), then at the 6-week follow-up (week 16)
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in self-reported depression symptoms as measured by Beck Depression Inventory (BDI-II).
時間枠：Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)
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As a secondary measure of depressive symptoms. Score scale from 0 (better outcome, no depression) to 63 (worst outcome, extreme depression). |
Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)
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Change in self-reported anxiety symptoms as measured by Beck Anxiety Inventory (BAI)
時間枠：Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)
|
As a secondary measure of anxiety symptoms. Score scale from 0 (better outcome, no depression) to 63 (worst outcome, extreme anxiety). |
Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)
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Change in self-reported suicidal thoughts symptoms as measured by Beck Scale for Suicidal Ideation (BSS)
時間枠：Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)
|
To assess the effect of treatment on suicidal thoughts that may be improved by iTBS. Score scale from 0 (better outcome, no desire for suicide) to 38 (worst outcome, extreme desire for suicide). |
Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)
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Change in self-reported hopelessness as measured by State Hope Scale (SHS)
時間枠：Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)
|
To assess the effect of treatment on self-report symptoms and perceptions of stress that may be improved by iTBS. 6-item measure where responses are rated on an 8-point Likert scale. Score scale from 1 (Definitely True) to 8 (Definitely False). |
Administered at screening, before the first iTBS treatment (week 4) and every week after that for 6 weeks (week 5, week 6, week 7, week 8, week 9, week 10), and at the 6-week follow-up assessment (week 16)
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Change in neuroplasticity as measured by neurophysiology (TMS) and MRI (Arterial Spin Labelling measures of brain blood flow)
時間枠：Administered at pre-assessment (baseline), before iTBS treatment course (week 4), end of iTBS treatment course (week 10)
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To assess the effect of treatment on biomarkers. Greater improvements in these biomarkers will also be associated with greater reductions in depressive symptoms. |
Administered at pre-assessment (baseline), before iTBS treatment course (week 4), end of iTBS treatment course (week 10)
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Change in grip strength as measured by dynamometer
時間枠：Administered at pre-assessment (baseline), before iTBS treatment course (week 4), end of iTBS treatment course (week 10), and at 6-week follow-up assessment (week 16)
|
To assess the effect of treatment on biomarkers. Greater improvements in these biomarkers will also be associated with greater reductions in depressive symptoms. |
Administered at pre-assessment (baseline), before iTBS treatment course (week 4), end of iTBS treatment course (week 10), and at 6-week follow-up assessment (week 16)
|
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Change in physical measures as assessed by anthropometrics
時間枠：Administered at pre-assessment (baseline), before iTBS treatment course (week 4), end of iTBS treatment course (week 10), and at 6-week follow-up assessment (week 16)
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To assess the effect of the intervention on physical health. |
Administered at pre-assessment (baseline), before iTBS treatment course (week 4), end of iTBS treatment course (week 10), and at 6-week follow-up assessment (week 16)
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Incidence of Treatment-Emergent Adverse Events
時間枠：Daily Monday-Friday throughout study (16 weeks).
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Adverse events will be tracked and recorded. |
Daily Monday-Friday throughout study (16 weeks).
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Side Effects
時間枠：Daily Monday-Friday throughout study (16 weeks).
|
Side effects will be tracked and recorded on any TMS visits, using the TMS side effects questionnaire. |
Daily Monday-Friday throughout study (16 weeks).
|
協力者と研究者
捜査官
- 主任研究者：Sara Tremblay, PhD、Royal Ottawa Mental Health Centre
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 0227
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
All Individual Participant Data collected from this study (IPD) will be de-identified for all parties who have permission to access it. This de-identified data may be shared with other researchers at the Royal's Institute of Mental Health Research. De-identified may be shared with the public only upon request. Please note that all data that has the potential of revealing participants' identity will NOT be used to share.
IPD 共有時間枠
De-identified data may become available (upon request) when the study is completed and published (anticipated time frame: the year of 2027)
IPD 共有アクセス基準
De-identified data will be accessible only through the permission of the lead research scientist. All requests must be made and accepted by her.
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