UMIN-CTR 臨床試験登録情報の閲覧

UMIN試験ID UMIN000006417
受付番号 R000007612
科学的試験名 うつ病個別化治療アルゴリズムの構築を目的とする遺伝子多型、定量脳波を用いた無作為割付臨床比較試験
一般公開日(本登録希望日) 2011/09/27
最終更新日 2023/10/07 10:10:08

※ 本ページ収載の情報は、臨床試験に関する情報公開を目的として、UMINが開設しているUMIN臨床試験登録システムに提供された臨床試験情報です。
※ 特定の医薬品や治療法等については、医療関係者や一般の方に向けて広告することは目的としていません。


基本情報/Basic information

一般向け試験名/Public title

日本語
うつ病個別化治療アルゴリズムの構築を目的とする遺伝子多型、定量脳波を用いた無作為割付臨床比較試験


英語
Investigation of biological and clinical predictor of antidepressant response for personalized medicine in depression ; a randomized controlled trial

一般向け試験名略称/Acronym

日本語
うつ病個別化治療アルゴリズムの構築を目的とするRCT研究


英語
Genotype Utility Needed for Depression Antidepressant Medication (GUNDAM)

科学的試験名/Scientific Title

日本語
うつ病個別化治療アルゴリズムの構築を目的とする遺伝子多型、定量脳波を用いた無作為割付臨床比較試験


英語
Investigation of biological and clinical predictor of antidepressant response for personalized medicine in depression ; a randomized controlled trial

科学的試験名略称/Scientific Title:Acronym

日本語
うつ病個別化治療アルゴリズムの構築を目的とするRCT研究


英語
Genotype Utility Needed for Depression Antidepressant Medication (GUNDAM)

試験実施地域/Region

日本/Japan


対象疾患/Condition

対象疾患名/Condition

日本語
うつ病


英語
Major depression

疾患区分1/Classification by specialty

精神神経科学/Psychiatry

疾患区分2/Classification by malignancy

悪性腫瘍以外/Others

ゲノム情報の取扱い/Genomic information

はい/YES


目的/Objectives

目的1/Narrative objectives1

日本語
治療選択肢が多様化している現在のうつ病治療において、患者背景、うつ病のサブタイプ、生物学的指標(遺伝子多型や脳波)に基づく各個人に適したうつ病の治療法、すなわち“うつ病個別化治療アルゴリズム”を作成する事を目的とする。


英語
Based on patient characteristics, subtype of depression and biological factor such as genetic factor and QEEG, we aimed to develop the personalized medicine and prescribed best therapeutic tool for each patient. That is, to establish algorithm for treatment of depression.

目的2/Basic objectives2

安全性・有効性/Safety,Efficacy

目的2 -その他詳細/Basic objectives -Others

日本語


英語

試験の性質1/Trial characteristics_1


試験の性質2/Trial characteristics_2


試験のフェーズ/Developmental phase



評価/Assessment

主要アウトカム評価項目/Primary outcomes

日本語
うつ症状の改善(HAM-D)


英語
Improvement of depressive symptom assessed by HAM-D

副次アウトカム評価項目/Key secondary outcomes

日本語
副作用(UKU)
QIDS
NEO personality inventory
社会認知機能


英語
Adverse effect assessed by UKU
QIDS
NEO personality inventory
Social-cognitive function


基本事項/Base

試験の種類/Study type

介入/Interventional


試験デザイン/Study design

基本デザイン/Basic design

並行群間比較/Parallel

ランダム化/Randomization

ランダム化/Randomized

ランダム化の単位/Randomization unit

個別/Individual

ブラインド化/Blinding

オープン/Open -no one is blinded

コントロール/Control

実薬・標準治療対照/Active

層別化/Stratification

はい/YES

動的割付/Dynamic allocation

いいえ/NO

試験実施施設の考慮/Institution consideration


ブロック化/Blocking


割付コードを知る方法/Concealment

封筒法/Numbered container method


介入/Intervention

群数/No. of arms

3

介入の目的/Purpose of intervention

治療・ケア/Treatment

介入の種類/Type of intervention

医薬品/Medicine

介入1/Interventions/Control_1

日本語
うつ病患者に無作為にミルタザピンもしくは選択的セロトニン再取り込み阻害薬(SSRI)を割り付ける


英語
Depressive patients are randomly assigned to either mirtazapine or
SSRIs.

介入2/Interventions/Control_2

日本語
治療4週後Non-response群は、無作為に補充療法を行う群と行わない群に振り分ける


英語
Non-responders after 4-week treatment are randomly assigned to either maintain the same treatment or augmentation.

介入3/Interventions/Control_3

日本語
治療8週後Non-remission群は、補充療法を行う


英語
Augmentation therapy are added to the subject who does not remit after 8-week treatment.

介入4/Interventions/Control_4

日本語


英語

介入5/Interventions/Control_5

日本語


英語

介入6/Interventions/Control_6

日本語


英語

介入7/Interventions/Control_7

日本語


英語

介入8/Interventions/Control_8

日本語


英語

介入9/Interventions/Control_9

日本語


英語

介入10/Interventions/Control_10

日本語


英語


適格性/Eligibility

年齢(下限)/Age-lower limit

18 歳/years-old 以上/<=

年齢(上限)/Age-upper limit

75 歳/years-old 以下/>=

性別/Gender

男女両方/Male and Female

選択基準/Key inclusion criteria

日本語
現在の病相が未治療(4週以上抗うつ薬が未投与)であるDSM―IVの大うつ病性障害の診断基準を満たす(原則としてHAM-D21項目 14点以上)18歳以上75歳未満の患者


英語
Drug naive patient (between 18 and 75 years old) with depression defined by DSN-IV whose HAM-D score are at least 14 .

除外基準/Key exclusion criteria

日本語
DSM-IVで大うつ病以外のI軸診断基準を満たすもの、てんかん、痙攣性疾患、脳器質性疾患、アルコール依存、薬物依存、甲状腺機能亢進症など重篤なホルモン異常、重篤な心・肝・腎機能障害または造血器障害、試験薬剤の成分に対し過敏症の既往歴を有する患者、試験薬剤投与前3ヵ月以内に電気ショック療法を受けた患者、妊婦,授乳婦または妊娠している可能性のある患者、試験期間中に妊娠を希望する患者、その他,担当医師が不適当とした患者


英語
Subjects with clinically significant unstable medical illness, pregnancy, a principal psychiatric diagnosis other than major depression, a history of substance abuse or dependence active within the previous 6 months, and electroconvulsive therapy within the previous 6 months were excluded.

目標参加者数/Target sample size

300


責任研究者/Research contact person

責任研究者/Name of lead principal investigator

日本語
正樹
ミドルネーム
加藤 


英語
Masaki
ミドルネーム
Kato

所属組織/Organization

日本語
関西医科大学


英語
Kansai Medical University

所属部署/Division name

日本語
精神神経科


英語
Department of Neuropsychiatry

郵便番号/Zip code

570-8506

住所/Address

日本語
大阪府守口市文園町10-15


英語
10-15 Fumizonocho Moriguchi, Osaka

電話/TEL

69921001

Email/Email

pangaea1975@yahoo.co.jp


試験問い合わせ窓口/Public contact

試験問い合わせ窓口担当者/Name of contact person

日本語
正樹
ミドルネーム
加藤 


英語
Masaki
ミドルネーム
Kato

組織名/Organization

日本語
関西医科大学


英語
Kansai Medical University

部署名/Division name

日本語
精神神経科


英語
Department of Neuropsychiatry

郵便番号/Zip code

570-8506

住所/Address

日本語
大阪府守口市文園町10-15


英語
10-15, Fumizono-cho, Moriguchi City, Osaka

電話/TEL

69921001

試験のホームページURL/Homepage URL


Email/Email

pangaea1975@yahoo.co.jp


実施責任個人または組織/Sponsor or person

機関名/Institute

日本語
その他


英語
Kansai Medical University Department of Neuropsychiatry

機関名/Institute
(機関選択不可の場合)

日本語
関西医科大学精神神経科


部署名/Department

日本語


個人名/Personal name

日本語


英語


研究費提供組織/Funding Source

機関名/Organization

日本語
その他


英語
Self funding, Ministry for Scientific Research,SENSHIN Medical Research Foundation

機関名/Organization
(機関選択不可の場合)

日本語
自己調達、先進医薬研究振興財団, 文部科学省科学研究費


組織名/Division

日本語


組織の区分/Category of Funding Organization

その他/Other

研究費拠出国/Nationality of Funding Organization

日本語


英語


その他の関連組織/Other related organizations

共同実施組織/Co-sponsor

日本語


英語

その他の研究費提供組織/Name of secondary funder(s)

日本語


英語


IRB等連絡先(公開)/IRB Contact (For public release)

組織名/Organization

日本語
関西医科大学医学倫理審査委員会


英語
Medical Ethics Review Committee, Kansai Medical University

住所/Address

日本語
大阪府守口市文園町10番15号


英語
10-15 Fumizonocho Moriguchi, Osaka

電話/Tel

06-6992-1001

Email/Email

katom@takii.kmu.ac.jp


他機関から発行された試験ID/Secondary IDs

他機関から発行された試験ID/Secondary IDs

いいえ/NO

試験ID1/Study ID_1


ID発行機関1/Org. issuing International ID_1

日本語


英語

試験ID2/Study ID_2


ID発行機関2/Org. issuing International ID_2

日本語


英語

治験届/IND to MHLW



試験実施施設/Institutions

試験実施施設名称/Institutions

関西医科大学付属滝井病院精神神経科(大阪府)


その他の管理情報/Other administrative information

一般公開日(本登録希望日)/Date of disclosure of the study information

2011 09 27


関連情報/Related information

プロトコル掲載URL/URL releasing protocol

http://www.journalofpsychiatricresearch.com/article/S0022-3956(16)30826-3/fulltext

試験結果の公開状況/Publication of results

最終結果が公表されている/Published


結果/Result

結果掲載URL/URL related to results and publications

http://www.journalofpsychiatricresearch.com/article/S0022-3956(16)30826-3/fulltext

組み入れ参加者数/Number of participants that the trial has enrolled

154

主な結果/Results

日本語
Mirtazapine showed significantly faster improvement compared to SSRIs. Somnolence rate was higher in mirtazapine and nausea rate was higher in SSRIs. Combination therapy showed a more favorable time course than SSRIs monotherapy.


英語
Mirtazapine showed significantly faster improvement compared to SSRIs. Somnolence rate was higher in mirtazapine and nausea rate was higher in SSRIs. Combination therapy showed a more favorable time course than SSRIs monotherapy.

主な結果入力日/Results date posted

2023 10 07

結果掲載遅延/Results Delayed


結果遅延理由/Results Delay Reason

日本語


英語

最初の試験結果の出版日/Date of the first journal publication of results


参加者背景/Baseline Characteristics

日本語
From September 2011 through December 2014, a total of 207 patients were screened, 154 were enrolled and 141 took at least one post baseline HAM-D assessment during the step I study. Out of 126 patients who completed step I, 58 patient failed to reach response and were randomly assigned again and 45 patients (mirtazapine; n=13, SSRIs; n=12 and combination; n=20) had at least one post 4-week HAM-D assessment during the step IIa. On the other hand, 68 patients (mirtazapine; n=30 and SSRIs; n=38) reached response during the step I study and 66 patients continued the same SSRIs/mirtazapine monotherapy for another 4 weeks in step IIb. The baseline clinical and sociodemographic characteristics of subjects are presented in table 1. The mean age was 47.2 years, 48.9% were female and 22.7% were unemployed. Participants had moderate-to-severe depression, as indicated by a mean HAM-D17 score of 20.7 points. Over one-third had recurrent depression. Duration of current MDD episode was 8 months, total duration of MDD was 3.9 years and age at first episode was 43 years.


英語
From September 2011 through December 2014, a total of 207 patients were screened, 154 were enrolled and 141 took at least one post baseline HAM-D assessment during the step I study. Out of 126 patients who completed step I, 58 patient failed to reach response and were randomly assigned again and 45 patients (mirtazapine; n=13, SSRIs; n=12 and combination; n=20) had at least one post 4-week HAM-D assessment during the step IIa. On the other hand, 68 patients (mirtazapine; n=30 and SSRIs; n=38) reached response during the step I study and 66 patients continued the same SSRIs/mirtazapine monotherapy for another 4 weeks in step IIb. The baseline clinical and sociodemographic characteristics of subjects are presented in table 1. The mean age was 47.2 years, 48.9% were female and 22.7% were unemployed. Participants had moderate-to-severe depression, as indicated by a mean HAM-D17 score of 20.7 points. Over one-third had recurrent depression. Duration of current MDD episode was 8 months, total duration of MDD was 3.9 years and age at first episode was 43 years.

参加者の流れ/Participant flow

日本語
Participants
The subjects included to the study were 20-75 years old outpatients, met the diagnosis of major depressive disorder according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders (American Psychiatric Association, 1994), Japanese, scoring at least 14 in the 17-item Hamilton Rating Scale for Depression (HAM-D 17) (Hamilton, 1967) and had been free of psychotropic drugs for at least 14 days before entering into the study. Subjects with clinically significant unstable medical illness, pregnancy, a principal psychiatric diagnosis other than major depression, a history of substance abuse or dependence active within the previous 6 months, and electroconvulsive therapy within the previous 6 months were excluded. The diagnoses were assigned by 2 independent senior psychiatrists and confirmed by a third psychiatrist.
Protocol treatment
In step I study, participants were randomly assigned to treatment with one of two classes of antidepressant; mirtazapine or SSRIs (paroxetine or sertraline) in a 1:1 ratio (Figure 1). Mirtazapine was administered once daily at bedtime and paroxetine and sertraline was administered once daily after dinner. The initial dose was 15mg/day for mirtazapine, 10 mg/day for paroxetine and 25 mg/day for sertraline. The dose must be increased to 30 mg/day for mirtazapine, 20mg/day for paroxetine and 50mg/day for sertraline within 2weeks and could be increased up to 45mg/day for mirtazapine, 40mg/day for paroxetine and 100 mg/day for sertraline in 4 weeks (maximum dose approved in Japan).
In step II study, patients who reached response, defined as an at least 50% decrease or remission, defined as 7 or less in HAM-D 17 total score after 4 weeks medication, continued the same monotherapy (Step IIb) and patients who failed to reach response or remission after 4 weeks, were randomly assigned to continue mirtazapine/ SSRIs monotherapy or combine them (Step IIa). Additional antidepressant was increased to minimally-effective dose (mirtazapine 30mg/day, paroxetine 20mg/day and sertraline 50mg/day) and could be adjusted based on clinical symptoms.
Concomitant psychotropic drugs were not allowed, except a low dose of sleep aids at bedtime for both Steps I and II. The patients' adherence to the study medication was monitored by counting the returned tablets and the patients' reports of non-adherence.


英語
Participants
The subjects included to the study were 20-75 years old outpatients, met the diagnosis of major depressive disorder according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders (American Psychiatric Association, 1994), Japanese, scoring at least 14 in the 17-item Hamilton Rating Scale for Depression (HAM-D 17) (Hamilton, 1967) and had been free of psychotropic drugs for at least 14 days before entering into the study. Subjects with clinically significant unstable medical illness, pregnancy, a principal psychiatric diagnosis other than major depression, a history of substance abuse or dependence active within the previous 6 months, and electroconvulsive therapy within the previous 6 months were excluded. The diagnoses were assigned by 2 independent senior psychiatrists and confirmed by a third psychiatrist.
Protocol treatment
In step I study, participants were randomly assigned to treatment with one of two classes of antidepressant; mirtazapine or SSRIs (paroxetine or sertraline) in a 1:1 ratio (Figure 1). Mirtazapine was administered once daily at bedtime and paroxetine and sertraline was administered once daily after dinner. The initial dose was 15mg/day for mirtazapine, 10 mg/day for paroxetine and 25 mg/day for sertraline. The dose must be increased to 30 mg/day for mirtazapine, 20mg/day for paroxetine and 50mg/day for sertraline within 2weeks and could be increased up to 45mg/day for mirtazapine, 40mg/day for paroxetine and 100 mg/day for sertraline in 4 weeks (maximum dose approved in Japan).
In step II study, patients who reached response, defined as an at least 50% decrease or remission, defined as 7 or less in HAM-D 17 total score after 4 weeks medication, continued the same monotherapy (Step IIb) and patients who failed to reach response or remission after 4 weeks, were randomly assigned to continue mirtazapine/ SSRIs monotherapy or combine them (Step IIa). Additional antidepressant was increased to minimally-effective dose (mirtazapine 30mg/day, paroxetine 20mg/day and sertraline 50mg/day) and could be adjusted based on clinical symptoms.
Concomitant psychotropic drugs were not allowed, except a low dose of sleep aids at bedtime for both Steps I and II. The patients' adherence to the study medication was monitored by counting the returned tablets and the patients' reports of non-adherence.

有害事象/Adverse events

日本語
Rate of sleepiness/sedation was significantly higher in mirtazapine prescribed subject (40.3%) compared to SSRIs (18.1%). Logistic regression analysis showed that mirtazapine (p=0.004, OR=3.3 95%CI=1.5-7.6) and male sex (p<0.001, OR=4.6 95%CI=1.9-10.7) contributed significantly to the higher rate of this adverse evet. But no difference was observed for more than 2 points worsening in rate of sleepiness/sedation between treatment groups (MIR=7.5%, SSRIs= 2.8%). Rate of nausea/vomiting was not observed for mirtazapine and this was significantly lower (p<0.0001) than for SSRIs (19.4%). For SSRIs, the rate of 2 point worsening was 6.9%. Both the rate of accommodation disturbances and erectile dysfunction/dry vagina for mirtazapine group was 0% and lower than SSRIs group (6.9% and 5.6%, respectively), but this differences were not statistically significant. Rate of drop out by any reason and by adverse event were 18.2% (mirtazapine=22.1%, SSRIs=14.3%) and 13.0% (mirtazapine=15.1%, SSRIs=10.1%), respectively without significant difference between treatment groups. No significant difference was observed for any other adverse event.


英語
Rate of sleepiness/sedation was significantly higher in mirtazapine prescribed subject (40.3%) compared to SSRIs (18.1%). Logistic regression analysis showed that mirtazapine (p=0.004, OR=3.3 95%CI=1.5-7.6) and male sex (p<0.001, OR=4.6 95%CI=1.9-10.7) contributed significantly to the higher rate of this adverse evet. But no difference was observed for more than 2 points worsening in rate of sleepiness/sedation between treatment groups (MIR=7.5%, SSRIs= 2.8%). Rate of nausea/vomiting was not observed for mirtazapine and this was significantly lower (p<0.0001) than for SSRIs (19.4%). For SSRIs, the rate of 2 point worsening was 6.9%. Both the rate of accommodation disturbances and erectile dysfunction/dry vagina for mirtazapine group was 0% and lower than SSRIs group (6.9% and 5.6%, respectively), but this differences were not statistically significant. Rate of drop out by any reason and by adverse event were 18.2% (mirtazapine=22.1%, SSRIs=14.3%) and 13.0% (mirtazapine=15.1%, SSRIs=10.1%), respectively without significant difference between treatment groups. No significant difference was observed for any other adverse event.

評価項目/Outcome measures

日本語
Treatment outcome measure
All patients were evaluated at baseline and bi-weekly thereafter until the end of the study using the HAM-D 17. The primary efficacy outcome was change in HAM-D 17 total score from baseline to week 4 for step I and from week 4 to week 8 for step II study. Secondary efficacy outcomes were rate of remission, defined as HAMD17 score <7, at week 2, 4, 6 and 8 and also the rate of response defined as a 50% decrease in severity from baseline at week 2 and 4. The HAM-D assessment was performed by trained senior psychiatrists (M.K., S.S., H.B., K.N. and Y.T.).

Side effect and adverse event measure
All adverse events volunteered or observed during the study were recorded, together with their severity and duration. The use of the Udvalg for Kliniske Undersogelser (UKU) side effect rating scale at baseline and bi-weekly ensured systematic collection of adverse events data. Other safety measures included 12-lead ECG and clinical laboratory assessments (hematology and serum chemistry) at baseline, week 4 and week8.


英語
Treatment outcome measure
All patients were evaluated at baseline and bi-weekly thereafter until the end of the study using the HAM-D 17. The primary efficacy outcome was change in HAM-D 17 total score from baseline to week 4 for step I and from week 4 to week 8 for step II study. Secondary efficacy outcomes were rate of remission, defined as HAMD17 score <7, at week 2, 4, 6 and 8 and also the rate of response defined as a 50% decrease in severity from baseline at week 2 and 4. The HAM-D assessment was performed by trained senior psychiatrists (M.K., S.S., H.B., K.N. and Y.T.).

Side effect and adverse event measure
All adverse events volunteered or observed during the study were recorded, together with their severity and duration. The use of the Udvalg for Kliniske Undersogelser (UKU) side effect rating scale at baseline and bi-weekly ensured systematic collection of adverse events data. Other safety measures included 12-lead ECG and clinical laboratory assessments (hematology and serum chemistry) at baseline, week 4 and week8.

個別症例データ共有計画/Plan to share IPD

日本語


英語

個別症例データ共有計画の詳細/IPD sharing Plan description

日本語


英語


試験進捗状況/Progress

試験進捗状況/Recruitment status

主たる結果の公表済み/Main results already published

プロトコル確定日/Date of protocol fixation

2011 01 01

倫理委員会による承認日/Date of IRB

2011 02 03

登録・組入れ開始(予定)日/Anticipated trial start date

2011 09 01

フォロー終了(予定)日/Last follow-up date

2015 04 30

入力終了(予定)日/Date of closure to data entry


データ固定(予定)日/Date trial data considered complete


解析終了(予定)日/Date analysis concluded



その他/Other

その他関連情報/Other related information

日本語


英語


管理情報/Management information

登録日時/Registered date

2011 09 27

最終更新日/Last modified on

2023 10 07



閲覧ページへのリンク/Link to view the page

日本語
https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000007612


英語
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007612


研究計画書
登録日時 ファイル名

研究症例データ仕様書
登録日時 ファイル名

研究症例データ
登録日時 ファイル名