UMIN-CTR Clinical Trial

Public title

Study of mechanisms by which Melsmon improves climacteric symptoms

Acronym

Mechanisms of action of Melsmon

Scientific Title

Study of mechanisms by which Melsmon improves climacteric symptoms

Scientific Title:Acronym

Mechanisms of action of Melsmon

Region

Japan

Condition

Climacteric syndrome

Classification by specialty

Medicine in general	Obstetrics and Gynecology	Psychiatry

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

1. To determine by analyzing simplified menopausal indices (SMI) whether climacteric symptoms in women in perimenopausal or postmenopausal period are improved by subcutaneous injection of Melsmon.
2. To measure various biochemical indices in peripheral blood that will be collected from participants before and after Melsmon injection
3. To determine correlations between improvement of SMI scores and parameters for oxidative stress conditions in blood
4. To explore plasma proteins that are involved in the improvement of SMI scores.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

This was a crossover study including a total of 31 patients which consisted 17 subjects of group 1 and 14 subjects in group 2. A first phase of the study consisted of blood collection and simplified menopausal indices (SMI) from patients of group 1 (or group 2) was measured for each patient before receiving Melsmon (or saline as a placebo). Patients of group 1 then received subcutaneous injection of Melsmon twice a week at a dose of 4 mL, irrespective of body weight, for 3 weeks consecutively. The primary outcome was to investigate the changes of SMIs following Melsmon injection and blood was also collected from all patients. After a washout period of one month blood samples were again collected and SMIs were determined from all patients of group 1. Next, injection of saline as a control of Melsmon was performed for l7 patients of group 1 by the same protocol stated above followed by a month of washout period. 14 patients of group 2 were treated with the same protocol stated group 2 followed by a first injection of saline.
SMI scores before and after Melsmon or saline injections were analyzed using a standard crossover statistical analysis by SPSS.

Key secondary outcomes

A second outcome was to determine whether the levels of alteration of SMI scores are correlated with the levels of oxidative stress or with any other biochemical parameters in peripheral blood. About 10 mL blood was collected from all the subjects of both groups before and after the injection of Melsmon or saline. Plasma and serum were prepared from the blood immediately. Oxidative/anti-oxidative parameters were analyzed and it was determined whether there are correlations between SMI scores and the parameters relevant to oxidative/anti-oxidative states. To determine whether plasma proteins that were related to alterations of SMI scores, 6 biochemical parameters including Alb, ALT, CK, AMY, HDL, and LDL in serum were analyzed.

Study type

Interventional

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Single blind -participants are blinded

Control

Placebo

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as a block.

Blocking

YES

Concealment

Pseudo-randomization

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Crossover comparison study 1;
Group 1: Phase 1 consisted of SMI measurement and blood collection prior to the initiation of the study, which was followed by Melsmon injection (4 mL/day x 2 days/week for 3 weeks). After completion of Melsmon injection, SMI scores were measured and blood samples were collected from all patients. Phase 2 included a month washout period, which was subsequently followed by the determination of SMI scores and blood collection. Saline was then injected into patients using the same protocol for Melsmon administration. Then SMI scores were again measured and blood samples were collected.

Interventions/Control_2

Crossover comparison study 2:
Group 2: Phase 1 consisted of SMI measurement and blood collection prior to the initiation of the study, which was followed by saline injection (4 mL/day x 2 days/week for 3 weeks). After completion of saline injection, SMI scores were measured and blood samples were collected from all patients. Phase 2 included a month washout period, which was subsequently followed by the determination of SMI scores and blood collection. Melsmon was then injected into patients using the same protocol for saline administration. Then SMI scores were again measured and blood samples were collected.

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

25

years-old

<=

Age-upper limit

70

years-old

>=

Gender

Female

Key inclusion criteria

Participants of the study were selected from outpatients, who are diagnosed climacteric syndrome or its related disorders with SMI scores higher than 29. Eligible participants should provide a written informed consent prior to participating in the study and must not have any of the exclusion criteria stated below.

Key exclusion criteria

The following subjects.
1) pregnant subjects or those with desire of pregnancy.
2) subjects of breast feeding
3) subjects taking female hormone medications
4) subjects taking medications affecting female hormone levels
5) subjects taking placental extract-containing drugs or supplements.
6) female hormone drugs or drugs affecting the female hormone state used within a month.
7) difficult of providing a written informed consent.
8) suffering from severe systemic disorders.
9) subjects who are under certain medical conditions and judged by doctor incompatible with the study.
10) subjects who have experience of drug allergy.
11) subjects who are judged inappropriate by doctors in the clinic.

Target sample size

31

Name of lead principal investigator

1st name
Middle name
Last name	1)Mahiko Nagase, 2)Ryoki Takahashi

Organization

1)Kichijoji Traditional Chinese Medicine Clinic.
2)Melsmon Pharmaceutical Co., Ltd.

Division name

1) Clinic. 2) Research Laboratory.

Zip code

Address

1) 1-13-6-5F Kichijoji, Musashino-shi, Tokyo 180-0004, Japan 2)Horikoshi building 3F, 39-1, 2 chome Ikebukuro, Toshima-ku, Tokyo 171-0014, Japan

TEL

0422-20-4110

Email

mahiko@kca.biglobe.ne.jp

Name of contact person

1st name
Middle name
Last name	Mahiko Nagase

Organization

Kichijoji Traditional Chinese Medicine Clinic.

Division name

Clinic

Zip code

Address

1-13-6-5F Kichijoji, Musashino-shi, Tokyo 180-0004, Japan

TEL

0422-20-4110

Homepage URL

Email

mahiko@kca.biglobe.ne.jp

Institute

Melsmon Pharmaceutical Co., Ltd
Research Laboratory

Institute

Department

Personal name

Organization

Melsmon Pharmaceutical Co., Ltd
Research Laboratory

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

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

吉祥寺中医クリニック(東京都）/Kichijoji Traditional Chinese Medicine Clinic (Tokyo).
メルスモン製薬株式会社（東京都）/Melsmon Pharmaceutical Co., Ltd (Tokyo)
Research Laboratory.

Date of disclosure of the study information

2018

Year

12

Month

31

Day

URL releasing protocol

Study of mechanisms by which Melsmon improves climacteric symptoms

Publication of results

Unpublished

URL related to results and publications

Study of mechanisms by which Melsmon improves climacteric symptoms

Number of participants that the trial has enrolled

30

Results

(Result 1)
No significant difference of all evalusted item between group 1 (n=17) and group 2 (n=13) before the clinical examination.

(Result 2)
we detected significant difference (p vs. placebo) following the eveluted item due to treatment with Melsmon.
Simple menoppausalIndex (SMI);Total SMI (p<0.001). psychological SMI (p=0.011), somatic SMI (p=0.003).

blood LDL decrease in the 1st term (p=0.039).

Results date posted

2019

Year

12

Month

19

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

30 Women (age 47.3+/-10.4) who has outpatients with climactical disorders or its doubtful symptom, participated in the study. all participants signed the consent record after an explanation of an imformed consent according to the Helsinki declaration.

Participant flow

All participants were not fallen out during the study. After the clinical examination a followup performed for 6 month. All participants asked QOL questions (SF36) 1 month after the end of the examination.

Adverse events

No adverse events were reported during the clinical examination and also after the examination for 6 month.

Outcome measures

Simple menoppausalIndex (SMI) and its subscale. blood biochemical nalalysis and blood ani-oxidative test.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Terminated

Date of protocol fixation

2016

Year

12

Month

28

Day

Date of IRB

2017

Year

01

Month

31

Day

Anticipated trial start date

2017

Year

02

Month

01

Day

Last follow-up date

2018

Year

04

Month

15

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

2018

Year

04

Month

15

Day

Other related information

Registered date

2017

Year

12

Month

16

Day

Last modified on

2019

Year

12

Month

19

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034401