UMIN-CTR Clinical Trial

Public title

Phase IIb clinical trial of steroid therapy in patients with HAM

Acronym

HAMLET-P

Scientific Title

Phase IIb clinical trial of steroid therapy in patients with HAM

Scientific Title:Acronym

HAMLET-P

Region

Japan

Condition

HTLV-1-Associated-Myelopathy Tropical Spastic Paraparesis (HAM/TSP)

Classification by specialty

Neurology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the effectiveness of the Methylprednisolone therapy to the Prednisolone oral treatment in rapid progressive patients with HAM/TSP.
To evaluate the safety of the Methylprednisolone therapy and the Prednisolone therapy in rapid progressive patients with HAM/TSP.
To evaluate the effectiveness of the Prednisolone therapy in rapid progressive patients with HAM/TSP.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase II,III

Primary outcomes

Efficacy:Presence or absence of 30% or more improvement in a walking time of 10-meter walk test or one grade or more improvement in OMDS at 15 days compared with baseline level.

Key secondary outcomes

Efficacy:
-A walking time of 10-meter walk test.
1. Presence or absence of 30% or more improvement in a walking time of 10-meter walk test.
2. An area under the curve from at 15 days and 29 days (4 weeks) compared with baseline level.
3. A variation at 15 days and 29 days (4 weeks) compared with baseline level.
-A walking distance for 2 or 6 minutes.
1. An area under the curve from at 15 days and 29 days (4 weeks) compared with baseline level.
2. A variation at 15 days and 29 days (4 weeks) compared with baseline level.
-OMDS.
Presence or absence of one grade or more improvement in OMDS at 15 days compared with baseline level.
-A neopterin concentration in cerebrospinal fluid.
A variation at 15 days compared with baseline
-A ratio of subjects treated the Methylprednisolone pulse therapy from 29 days (4weeks) to 169 days (24 weeks).

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Dose comparison

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Following to administrate Methylprednisolone 1000mg/day intravenously slowly for consecutive three days, Prednisolone is administered orally for a maximum dose in 0.5mg/kg/day, then decreased gradually and terminated. There is a case to maintain the dose of Prednisolone by the degree of a progress of underlying disease.

Interventions/Control_2

Prednisolone is administered orally for a maximum dose in 0.5mg/kg/day, then decreased gradually and terminated. There is a case to maintain the dose of Prednisolone by the degree of a progress of underlying disease.

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

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1) The patient who has diagnosed with HAM based on the Belem criterion.
(2) The patient over 18 years of age at the day of giving informed consent.
(3) The patient who can walk more than 10 meters regardless of the necessity of walking aids at the day of giving informed consent. However, the use of the walk aid is allowed it less than two sticks. The use of the walker is possible.
(4) The patient that the main organ function is maintained. (To confirm by the most recent inspection data within 28 days of enrollment.)
1. Neutrophils: more than 1500/mm3
2. PLT: more than 100,000/mm3
3. Hb : more than 9.0 g/dL
4. AST: within 3 times of the upper limit of the institution criteria
5. ALT: within 3 times of the upper limit of the institution criteria
6. Serum Cre: within 3 times of the upper limit of the institution criteria
7. HbA1c: within 6.5 percent
(5) The patient or the legally acceptable representative gives of his/her own free will consent to participate this study.

(6) The patient that can come to the hospital for a treatment and a follow-up along the schedule of study.

Key exclusion criteria

(1)Patients who have received corticosteroids or other treatment targeted to HAM within 12 weeks prior to giving informed consent
(3)Patients who have undergone invasive surgeries requiring general anesthesia within 24 weeks prior to giving informed consent
(4)Patients who have participated in other treatment studies within 16 weeks prior to giving informed consent
(5)Patients who have undergone live or attenuated/inactivated vaccinations within four weeks of giving informed consent, or who plan to be vaccinated during the course of the study.
(6)Patients taking the ascorbic acid more than 1.5g/day, prosultiamine, or pentosan polysulfate within two weeks of giving informed consent.
(7)Patients with a history of acute myocardial infarction
(8)Patients with a history of tuberculosis or with active tuberculosis
(9)Patients with serious complicating conditions
(10)Patients with uncontrolled hypertension
(11)Patients with uncontrolled electrolyte imbalance
(12)Patients with thrombosis
(13)Patients with a history of cancer with complications
(14)Patients with peptic ulcer
(15)Patients with ATL
(16)Patients with poorly controlled eye disease
(17)Patients with a history of steroid-induced glaucoma
(18)Pregnant or breastfeeding women or patients who may become pregnant or withhold assent to prevention of conception by taking appropriate approach such as condom in cooperation with their partners during the study period
(19)Patients in whom assessment with the walk test is difficult or the symptoms can be worsened by the walk test
(20)Patients with neurological deficits or findings on MRI suggesting it due to disorders other than HAM

Target sample size

8

Name of lead principal investigator

1st name
Middle name
Last name	Yoshihisa Yamano M.D.,Ph.D.

Organization

St. Marianna University School of Medicine Hospital

Division name

Department of Neurology

Zip code

Address

2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8512 Japan

TEL

044-977-8111

Email

yyamano@marianna-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Ushitani,Kuwahara

Organization

HAMLET-P Coordinating Center

Division name

Clinical Research Data Center,St. Marianna University School of Medicine

Zip code

Address

2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511 Japan

TEL

044-977-8111(6191)

Homepage URL

Email

mariadc_ham@marianna-u.ac.jp

Institute

St. Marianna University School of Medicine Hospital

Institute

Department

Personal name

Organization

The Research on Measures for Intractable Diseases Project of Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

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

2016/08/03

Institutions

聖マリアンナ医科大学病院（神奈川県）

Date of disclosure of the study information

2016

Year

08

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

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

2016

Year

07

Month

04

Day

Date of IRB

2016

Year

07

Month

14

Day

Anticipated trial start date

2016

Year

08

Month

31

Day

Last follow-up date

2020

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

08

Month

28

Day

Last modified on

2022

Year

03

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027409