UMIN-CTR Clinical Trial

Public title

The elucidation of the action mechanism on the effectiveness of propagermanium for Crohn's disease

Acronym

The action mechanism of propagermanium for Crohn's disease (PROCD)

Scientific Title

The elucidation of the action mechanism on the effectiveness of propagermanium for Crohn's disease

Scientific Title:Acronym

The action mechanism of propagermanium for Crohn's disease (PROCD)

Region

Japan

Condition

Crohn's disease

Classification by specialty

Gastroenterology

Gastrointestinal surgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate that the efficacy of the organic germanium compound propagermanium for Crohn's disease (CD) using the blood or the resection specimens (intestine) from patients with CD.

Basic objectives2

Others

Basic objectives -Others

In a previous study, we found that propagermanium improved the pathological and intestinal lesion score in TNBS-induced colitis mice or rats, which shared pathological and immunological features with human CD. We speculated this effect caused by the inhibition of monocyte and/or macrophage migration in intestine by propagermanium, as reported before. Furthermore, we also obtained the data which suggests that propagermanium reduced the production of inflammatory cytokines which are reported as substantial cytokines for the etiology of CD.

We conducted to confirm whether the effects are represented in peripheral blood mononuclear cells (PBMC) or lamina propria mononuclear cells (LPMC), voluntary donated from the patients with CD.

This study was conducted in vitro setting and propagermanium was not administered to the patients with CD.

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

To confirm whether propagermanium inhibit the secretion of the inflammatory cytokines from LPS-stimulated human PBMC and LPMC.

Key secondary outcomes

To explore the clinical and the therapeutic background of responders to propagermanium.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

1.To collect approximately 20ml of peripheral blood from CD patients who are under medical examination and treatment in Hyogo College of Medicine.

2.To be provided approximately 30g of intestinal specimen from the patients with CD who undergoes intestinal resection in Hyogo College of Medicine.

Interventions/Control_2

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

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1.Patients who had a diagnosis of CD before participation to this study and who was able to provide written informed consent to be collected approximately 20ml of peripheral blood.

2.The CD patients who had necessity for intestinal resection because of exacerbation and who was able to provide written informed consent to provide approximately 30g of resected tissue in their surgery.

Key exclusion criteria

1.Patients who could not provide written informed consent to be provide peripheral blood or intestinal tissue.

2.Patient who was administrated high dose of corticosteroids.

Target sample size

40

Name of lead principal investigator

1st name
Middle name
Last name	Shiro Nakamura

Organization

Hyogo College of Medicine

Division name

Department of Inflammatory Bowel Disease, Division of Internal Medicine

Zip code

Address

1-1,Mukogawa, Nishinomiya, Hyogo, 663-8501

TEL

0798-45-6663

Email

shiro@hyo-med.ac.jp

Name of contact person

1st name
Middle name
Last name	Kazuko Nagase

Organization

Hyogo College of Medicine

Division name

Department of Inflammatory Bowel Disease, Division of Internal Medicine

Zip code

Address

1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501

TEL

0798-45-6663

Homepage URL

Email

kazuko@hyo-med.ac.jp

Institute

Hyogo College of Medicine, Department of Inflammatory Bowel Disease, Division of Internal Medicine

Institute

Department

Personal name

Organization

Sanwa Kagaku Kenkyusho Co,, Ltd.

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Japan

Co-sponsor

Sanwa Kagaku Kenkyusho Co,, Ltd.

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

兵庫医科医大学病院（兵庫県）
Hyogo College of Medicine

Date of disclosure of the study information

2014

Year

03

Month

28

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

Results

Experiment 1: The anti-inflammatory effect of PGe in PBMCs of CD patients.

We were provided with 28 PBMC samples from 26 patients with CD. PBMC samples were incubated with PGe at 2 μg/mL for one hour before being stimulated with LPS at 15pg/mL for another 24 hour. The supernatants were used as a source for the cytokines. TNF-α and IL-6 levels were assayed using enzyme immunoassay kits. Overall, PGe significantly reduced the production of TNF-α and IL-6 compared with samples without PGe as control test.

Experiment 2: The anti-inflammatory effect of PGe in LPMCs of CD patients.

We were provided with five intestinal specimens. LPMCs were isolated from the intestinal specimens by using a modified technique originally described by Kamada, et al. (Reference). Then we isolated CD14+CD33+ macrophages from LPMCs which were reported to produce pro-inflammatory cytokines including IL-23, TNF-α and IL-6 and have a key role in the pathogenesis of CD. However, we could not isolate enough CD14+CD33+ macrophages for the following experiment to show PGe's effects. In view of these limitations, we decided to discontinue experiment 2 using CD14+CD33+ macrophages isolated from LPMCs.

In conclusion, PGe reduced the production of inflammatory cytokines produced by CD patient's PBMCs. Accordingly, PGe seems to be a potential drug for IBD patients, especially, in the HBV carrier IBD patients or the patients who are intolerant to biological therapy.

The results of this study was presented in the poster session on The 101th general meeting of Japanese society of Gastroenterology 2015 on April 9th, 2015 held at Sendai, Miyagi, Japan.

Reference
Kamada N, Hisamatsu T, Okamoto S, et al. J Clin Invest. 2008 Jun;118(6):2269-80.

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

Main results already published

Date of protocol fixation

2012

Year

02

Month

09

Day

Date of IRB

Anticipated trial start date

2012

Year

03

Month

01

Day

Last follow-up date

2013

Year

12

Month

20

Day

Date of closure to data entry

2013

Year

12

Month

31

Day

Date trial data considered complete

2014

Year

02

Month

01

Day

Date analysis concluded

2014

Year

02

Month

28

Day

Other related information

1.The title of this study was differ from the title we have applied previously to IRB in Hyogo College of Medicine:The effectiveness of propagermanium for Crohn's disease. Since this study was not a clinical trial, but an in vitro study to elucidate the action mechanism on the effectiveness of propagermanium for CD using peripheral blood and intestinal tissue donated from patients with CD. To clarify this feature, we decided the title of this study as: The elucidation of the action mechanism on the effectiveness of propagermanium for Crohn's disease.

2. At first, we have assumed colitic cancer (CC) as control disease for CD, but there was no patients with CC who could participate to this study. For this reason, all participants in this study was patients with CD.

Registered date

2014

Year

03

Month

27

Day

Last modified on

2015

Year

10

Month

08

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015799