Study on iTBS Regulating the Reward Circuit Function to Improve Anhedonia in Depression (iTMMDD)
Study on the Efficacy of iTBS Targeting NAc and sgACC in Regulating the Reward Circuit Function to Improve Anhedonia in Depression
The goal of this clinical trial is to learn if the proposed intermittent theta burst stimulation (iTBS) protocol can effectively improve anhedonia symptoms in depressed patients. The stimulation targets in our protocol include (1) dual-target stimulation at the left dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). (2) single-target stimulation at the left DLPFC.
The main questions it aims to answer are:
- Whether iTBS of dual-target stimulation (left DLPFC and OFC) can improve the symptoms of anhedonia and better than single-target stimulation at the left DLPFC?
- Whether iTBS of the dual targets of left DLPFC and OFC can improve the symptoms of anhedonia by correcting the abnormal functional connectivity of DLPFC-NAc and OFC-sgACC, regulating the functional abnormalities of NAc and sgACC, and indirectly repairing the overall dysfunction of the reward circuit.
- Researchers will compare dual-target stimulation to single-target stimulation and sham dual-target stimulation (a dedicated sham coil is utilized which produces an identical audible click and physical sensation) to see if the proposed iTBS protocol works to treat anhedonia.
Participants will:
- Take 6 sessions of dual-target iTBS or single-target iTBS every day, for 5 consecutive days.
- Visit our hospital at 1 week, 4 weeks, and 8weeks after the iTBS treatment completion, for clinical evaluation and brain image examination.
調査の概要
詳細な説明
Anhedonia, defined as the diminished capacity to experience pleasure, is a core symptom of Major Depressive Disorder (MDD). Patients with anhedonia exhibit a pervasive loss of interest or pleasure in all or almost all previously enjoyable activities, which frequently leads to a profound reduction in the desire to engage in rewarding behaviors. Previous studies have reported that anhedonia occurs in 37% to 72% of depressed individuals. Patients with depression accompanied by anhedonia tend to respond poorly to medication and psychotherapy but show relatively better responses to conventional physical treatments such as electroconvulsive therapy (ECT). Research has shown that improving anhedonia significantly enhances social functioning in depressed patients. Therefore, more effective treatments targeting anhedonia are needed. Achieving breakthroughs in therapeutic approaches and understanding their underlying mechanisms will contribute substantially to progress in this field.
Theta-burst stimulation (TBS) utilizes a stimulation pattern that closely mimics the natural firing frequencies of cerebral neurons. Accumulating evidence has demonstrated the clinical efficacy of intermittent TBS (iTBS) in alleviating depressive symptoms. Thus, this study aims to investigate and evaluate whether the proposed iTBS protocol can effectively improve anhedonia symptoms in depressed patients by regulating functional abnormalities.
The stimulation targets in our protocol include (1) dual-target stimulation at the left dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). (2) single-target stimulation at the left DLPFC.
The main questions it aims to answer are:
- Whether iTBS of dual-target stimulation (left DLPFC and OFC) can improve the symptoms of anhedonia and better than single-target stimulation?
- Whether iTBS of the dual targets of left DLPFC and OFC can improve the anhedonia symptom by correcting the abnormal functional connectivity of DLPFC-NAc and OFC-sgACC, regulating the functional abnormalities of NAc and sgACC, and indirectly repairing the overall dysfunction of the reward circuit?
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：Wenbin Guo, PhD
- 電話番号：+86 73185360921
- メール：guowenbin76@csu.edu.cn
研究場所
-
-
Hunan
-
Changsha、Hunan、中国、410000
- 募集
- The Second Xiangya Hospital of Central South University
-
コンタクト：
- Meiqi Yan, Master
- 電話番号：+86 18155517736
- メール：meiqi7012@163.com
-
-
参加基準
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Aged 18-45 years, and right-handed;
- Diagnosed with major depressive disorder (MDD) by at least two qualified psychiatrists, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with a Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 20 or a 17-item Hamilton Depression Rating Scale (HAMD-17) score ≥ 17;
- Evaluated by a psychiatrist as having prominent anhedonia, and meeting the cutoff criteria on two self-report anhedonia scales, including a Snaith-Hamilton Pleasure Scale, Chinese version (SHAPS-C) score ≥ 20, or a Temporal Experience of Pleasure Scale, Chinese version (TEPS-C) score ≤ 76;
- Medication type and dosage remained unchanged for at least 4 weeks prior to treatment initiation and throughout the study period;
- MADRS item 10 score ≤ 4.
Exclusion Criteria:
- A history of epilepsy, seizures, stroke, or other serious organic brain diseases;
- Presence of severe infectious diseases, malignant tumors, or other major unstable medical conditions;
- Intellectual disability or developmental delay, presence of psychotic symptoms, or meeting the diagnostic criteria for other psychiatric disorders;
- A history of substance abuse or psychoactive substance use;
- Presence of intracranial implants (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes), or any other metallic objects in or near the head that cannot be safely removed (excluding dental fillings);
- Contraindications to MRI or structural intracranial abnormalities detected on MRI;
- Pregnant or breastfeeding women;
- Receipt of electroconvulsive therapy (ECT) within the past 6 months, or transcranial magnetic stimulation (TMS) within the past 3 months;
- Current daily use of lorazepam > 2 mg (or an equivalent dose), or use of antiepileptic drugs at any dose;
- Presence of strong suicidal ideation, or a MADRS item 10 score > 4.
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 |
|---|---|
|
実験的：Left DLPFC + OFC iTBS Group
iTBS Parameter Specifications: 60 cycles of 10 bursts of three pulses at 50 Hz were delivered in 2-second trains (5 Hz) with an 8-second intertrain interval. The total duration of a single session is 10 minutes, comprising 60 trains and yielding a total of 1,800 pulses per session. Treatment Protocol for Left DLPFC+OFC iTBS Group: Stimulations are first delivered to the left DLPFC-NAc functional region using the specified iTBS parameters (1,800 pulses per session), performed 3 sessions daily with a 50-minute interval between sessions. Subsequently, stimulation was applied to the left OFC-sgACC functional region with the identical parameters (1,800 pulses per session), also performed 3 sessions daily with a 50-minute interval. This yields a cumulative total of 10,800 pulses over 5 consecutive days, for a total of 54,000 pulses. |
iTBS Parameter Specifications: 60 cycles of 10 bursts of three pulses at 50 Hz were delivered in 2-second trains (5 Hz) with an 8-second intertrain interval.
The total duration of a single session is 10 minutes, comprising 60 trains and yielding a total of 1,800 pulses per session.
For the Left DLPFC + OFC iTBS Group, stimulation is first delivered to the left DLPFC-NAc functional region using the specified iTBS parameters (1,800 pulses per session), performed 3 sessions daily with a 50-minute interval between sessions.
Subsequently, stimulation is applied to the left OFC-sgACC functional region with the identical parameters (1,800 pulses per session), also performed 3 sessions daily with a 50-minute interval.
This yields a cumulative total of 10,800 pulses over 5 consecutive days, for a total of 54,000 pulses.
他の名前：
|
|
実験的：Left DLPFC iTBS Group
iTBS Parameter Specifications: 60 cycles of 10 bursts of three pulses at 50 Hz were delivered in 2-second trains (5 Hz) with an 8-second intertrain interval. The total duration of a single session is 10 minutes, comprising 60 trains and yielding a total of 1,800 pulses per session. Treatment Protocol for Left DLPFC iTBS Group: For Group B, stimulations are delivered solely to the left DLPFC-NAc functional region using the specified iTBS parameters, performed 6 sessions daily with a 50-minute interval between sessions. This yields a cumulative total of 10,800 pulses over 5 consecutive days, for a total of 54,000 pulses. |
iTBS Parameter Specifications: 60 cycles of 10 bursts of three pulses at 50 Hz were delivered in 2-second trains (5 Hz) with an 8-second intertrain interval.
The total duration of a single session is 10 minutes, comprising 60 trains and yielding a total of 1,800 pulses per session.
For the left DLPFC iTBS Group, stimulation is delivered solely to the left DLPFC-NAc functional region using the specified iTBS parameters, with 6 sessions performed daily, each with a 50-minute interval between sessions.
This yields a cumulative total of 10,800 pulses over 5 consecutive days, for a total of 54,000 pulses.
他の名前：
|
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 |
|---|---|---|
|
Total score of Montgomery-Åsberg Depression Rating Scale (MADRS)
時間枠：*Baseline; * Day 2- Day 6 (every treatment day); *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
The Montgomery-Åsberg Depression Rating Scale (MADRS) scores will be evaluated before and after treatment.
Total score: 0-60.
A higher score means worse depressive symptoms.
|
*Baseline; * Day 2- Day 6 (every treatment day); *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
|
Remission Rate of Montgomery-Åsberg Depression Rating Scale (MADRS) scores
時間枠：* Day 2- Day 6 (every treatment day); *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
The proportion of patients in each group achieving remission.
Remission is defined as a MADRS score < 11 points.
|
* Day 2- Day 6 (every treatment day); *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
|
Response Rate of Montgomery-Åsberg Depression Rating Scale (MADRS) scores
時間枠：* Day 2- Day 6 (every treatment day); *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
The percentage change in MADRS scores from baseline, calculated as [(MADRSpre - MADRSpost) / MADRSpre] * 100%.
|
* Day 2- Day 6 (every treatment day); *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Total score of the Temporal Experience of Pleasure Scale - Chinese Version (TEPS-C)
時間枠：*Baseline; *Day 6; *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
Total score: 20-120.
The lower score means worse anhedonia.
|
*Baseline; *Day 6; *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
|
Remission rate of Temporal Experience of Pleasure Scale - Chinese Version (TEPS-C) score
時間枠：*Day 6; *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
Remission means the TEPS-C score > 76.
The TEPS-C remission rate is the proportion of patients in each group whose TEPS-C scores increased to >76 after treatment.
|
*Day 6; *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Total score of the 17-item Hamilton Depression Rating Scale (HAMD-17)
時間枠：*Baseline; *Day 6; *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
Total score: 0-52.
A higher score means worse depressive symptoms.
|
*Baseline; *Day 6; *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
|
Total scores of the Chinese version of the Snaith-Hamilton Pleasure Scale (SHAPS-C) score
時間枠：*Baseline; *Day 6; *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
Total score: 14-56.
A higher score means worse anhedonia.
|
*Baseline; *Day 6; *1 week post-treatment; *4 weeks post-treatment; *8 weeks post-treatment.
|
|
Brain MRI
時間枠：*Baseline; *Day 6, up to 1day delay; *8 weeks post-treatment.
|
Resting-state magnetic resonance imaging scans will be conducted.
Resting-state functional connectivity (rs-FC) changes before and after treatment will be assessed by fMRI.
And its potential correlation with clinical symptom changes will be further explored.
|
*Baseline; *Day 6, up to 1day delay; *8 weeks post-treatment.
|
|
Questionnaire: The Beck Scale for Suicide Ideation (BSI) scores
時間枠：*Baseline; *Day 6; * 1 week post-treatment; * 4 weeks post-treatment; * 8 weeks post-treatment.
|
The Beck Scale for Suicide Ideation (BSI) scores will be evaluated before and after treatment.
Total score: 0-38.
Higher scores indicate greater severity of suicidal ideation.
|
*Baseline; *Day 6; * 1 week post-treatment; * 4 weeks post-treatment; * 8 weeks post-treatment.
|
|
Total Score of the Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS)
時間枠：*Baseline; *Day 6; * 8 weeks post-treatment.
|
The RBANS is an instrument used to assess cognitive functioning.
The Total Scale Score will be evaluated.
The standard score range is typically 40 to 160 (index score based).
A higher score indicates better cognitive performance.
|
*Baseline; *Day 6; * 8 weeks post-treatment.
|
|
Wisconsin Card Sorting Test (WCST) Perseverative Errors scores
時間枠：*Baseline; *Day 6; *8 weeks post-treatment.
|
The WCST is an assessment of executive function and cognitive flexibility.
This measure evaluates the number of perseverative errors, which occur when a participant continues to apply a previous sorting rule after the rule has changed.
For this 48-card version, the theoretical score ranges from 0 to 48.
A higher score indicates worse cognitive flexibility and greater executive dysfunction.
|
*Baseline; *Day 6; *8 weeks post-treatment.
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Wenbin Guo, PhD、Second Xiangya Hospital of Central South University
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
追加の関連 MeSH 用語
その他の研究ID番号
- LYG20260013
- ChiCTR2600125718 (レジストリ識別子：Chinese Clinical Trial Registry)
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
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。