UMIN-CTR Clinical Trial

Public title

Double-blind Trial with Rikkunshito versus Placebo on Efficacy and Safety
in Patients with Functional Dyspepsia :Multi-center Study

Acronym

DREAM Study

Scientific Title

Double-blind Trial with Rikkunshito versus Placebo on Efficacy and Safety
in Patients with Functional Dyspepsia :Multi-center Study

Scientific Title:Acronym

DREAM Study

Region

Japan

Condition

Functional Dyspepsia

Classification by specialty

Gastroenterology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The purpose of this study is to assess the efficacy and safety of rikkunshito compared to placebo in Japanese subjects with Functional Dyspepsia.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

Global assessment of overall treatment efficacy (OTE). At 4 and 8-week after treatment

Key secondary outcomes

Global overall symptom (GOS)
Modified frequency scale for the symptoms of GERD (Modified FSSG)
The patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM)
Hospital anxiety and depression scale (HADS)
Short-form health survy-8 (SF-8)

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is considered as a block.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Rikkunshito

Interventions/Control_2

Rikkunshito placebo

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1.Patients diagnosed with FD according
to the Rome III criteria
1) Criteria fulfilled for the last 3
months with symptom onset at least
6 months prior to diagnosis
2) Have not received upper endoscopy
within the last 6 months prior to
enrollment and do not have
evidence of structural/organic
disease
3) Must have one or more of the
following symptoms:
a) Bothersome postprandial fullness
b) Early satiation
c) Epigastric pain
d) Epigastric burning
2.At least one of the FD-related symptoms on the Global Overall Symptom (GOS) scale (bothersome postprandial fullness, early satiation, epigastric pain, epigastric burning) is >4, whereas heartburn is <3.
3.Total score of depression-related symptoms on Hospital Anxiety and Depression Score (HAD) is <10.
4.Age: Aged 20 and over
5.No criteria on sex.
6.Type of visit: Outpatient.
7.Provides voluntary informed consent after receiving adequate explanation and demonstrates thorough understanding of the nature of the study.

Key exclusion criteria

1.Confirmed ulcer (excluding scars) or malignant tumor in the upper GI.
2.Suspected organic lesions in the hepato-biliary-pancreatic regions such as cholelithiasis, hepatitis, pancreatitis.
3.History of upper GI resection.
4.Serious complications (liver, kidney, heart, or blood disease or metabolic disease).
5.Less than a year since testing positive for H. pylori or have undergone asuccessful eradication therapy.
6.Use of prohibited medications.
7.Neuropsychiatric disorders.
8.Use of or planned use of another
investigational drug.
9.Unable to take drugs orally.
10.History of allergic reactions to Kampo medicines.
11.Pregnant or lactating women or those who are planning to conceive during the study period.
12.Deemed ineligible by principal investigator or sub-investigator

Target sample size

460

Name of lead principal investigator

1st name
Middle name
Last name	Tetsuo Arakawa

Organization

Osaka City University (President)

Division name

Department of Gastroenterology

Zip code

Address

3-3-138, Sugimoto, Sumiyoshi-ku, Osaka

TEL

06-8805-2000

Email

arakawa@ad.osaka-cu.ac.jp

Name of contact person

1st name
Middle name
Last name	Kazunari Tominaga

Organization

Osaka Medical College

Division name

Department of Gastroenterology

Zip code

Address

2-7, Daigaku-machi, Takatsuki-shi, Osaka

TEL

072-683-1221

Homepage URL

Email

in2139@osaka-med.ac.jp

Institute

DREAM study group

Institute

Department

Personal name

Organization

The Waksman Foundation of Japan INC

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

NCT02037776

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

北海道大学病院（北海道） 　岩手医科大学病院（岩手県）
群馬大学医学部附属病院（群馬県）　順天堂大学医学部附属順天堂医院（東京都）
杏林大学医学部付属病院（東京都）　千葉大学医学部附属病院（千葉県）
日本医科大学付属病院（東京都）　　大阪市立大学医学部附属病院（大阪府）
浜松医科大学医学部附属病院（静岡県）　兵庫医科大学病院（兵庫県）
大阪医科大学附属病院（大阪府） 　島根大学医学部附属病院（島根県）
川崎医科大学附属病院（岡山県）　　熊本大学医学部附属病院（熊本県）
佐賀大学医学部附属病院（佐賀県）　大分大学医学部附属病院（大分県）

Date of disclosure of the study information

2014

Year

03

Month

31

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

In this study, 128 patients were included in the safety analysis set and 125 were included in the full analysis set (FAS). As for demographic characteristics in the FAS, there were more women (89 patients) than men (36 patients); mean age was 50.4; mean BMI was 21.2 kg/m²; 82 patients had duration of FD >1 year. Regarding a subtype of FD, 49 patients had a PDS subtype, 42 had an EPS, and 34 had overlapping PDS-EPS. A total of 114 patients had no overlapping with IBS.

In the analysis of the score distribution of 7 categories in OTE at the final data (i.e., the latest evaluable time point of the all patients including discontinued patients) in the FAS, a primary endpoint of this study, the patients in Rikkunshito group ranged between score 1 and 4, those in Rikkunshito placebo group (including those worsened) ranged between score 1 and 5, and statistically significant differences were observed (p=0.038).
In the secondary endpoints, changes from baseline at the final data were statistically significant differences between groups in a total scores of Modified FSSG, GOS score, subscores of Postprandial Fullness/Early satiety and Bloating in PAGI-SYM, as well as overall score and Anxiety subscore of HAD. No statistical differences were observed in either PCS or MCS score of SF-8.

In the safety analysis set, the incidence of AEs was 10.8% (7/65 patients) in Rikkunshito group and 11.1% (7/63) in Rikkunshito placebo group. The most common AEs reported by SOC were Gastrointestinal disorders in the both groups (4 patients in Rikkunshito group, 3 in Rikkunshito placebo group). The incidence of ADRs was 4.6% (constipation, diarrhoea, and faeces soft, 1 patient each) in Rikkunshito group and 1.6% (rush, 1 patient) in Rikkunshito placebo group. SAEs were reported from 2 patients in Rikkunshito placebo group (cervix carcinoma, rush). No death occurred in this study.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2013

Year

10

Month

03

Day

Date of IRB

Anticipated trial start date

2014

Year

04

Month

03

Day

Last follow-up date

2016

Year

03

Month

25

Day

Date of closure to data entry

2016

Year

07

Month

11

Day

Date trial data considered complete

2016

Year

07

Month

27

Day

Date analysis concluded

2016

Year

12

Month

09

Day

Other related information

Registered date

2014

Year

01

Month

09

Day

Last modified on

2017

Year

02

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014957