UMIN-ICDS Clinical Trial

Public title

Random prospective study of lumbar-abdominal shunting for normal pressure hydrocephalus associated with Parkinson's disease.

Acronym

Shunt-PD study

Scientific Title

A controlled, randomized, parallel-group, prospective study of lumbar-abdominal shunting for normal pressure hydrocephalus complicated by Parkinson's disease and related disorders.

Scientific Title:Acronym

Shunt-PD study

Region

Japan

Condition

Parkinson's disease, Parkinson's disease with dementia, normal pressure hydrocephalus

Classification by specialty

Neurology

Neurosurgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Idiopathic Normal Pressure Hydrocephalus (iNPH) is a treatable neurological disorder characterized by dementia, urinary incontinence, and gait disturbance that can be corrected by lumboperiotoneal shunt(LPS) surgery. It is estimated that there are approximately 1 million patients with iNPH in Japan, and the number of patients with iNPH is increasing in Japan as the population ages. However, we conducted a retrospective study of iNPH patients hospitalized over the past 10 years and found that iNPH is associated with Parkinson's disease (PD) and its related disorder, dementia of Lewy bodies (DLB), as well as progressive supranuclear palsy (PSP). We reported that DAT scans are useful for detecting these complications. Furthermore, LPS surgery was partially effective not only in patients with iNPH but also in those with PD complicated by iNPH. However, clinically, it is often difficult to differentiate whether the case is complicated or uncomplicated, and the effectiveness is not consistent in AD. There is no clear conclusion whether that shunt surgery is really effective in PD and its related diseases.
The purpose of this study is to confirm the results of this retrospective study in a prospective study. This study will elucidate the correlation between the improvement in specific clinical symptoms and the improvement in imaging (Evans index, DAT-SPECT, etc.). In addition, iNPH will be shown to be a potential disease-modifying therapy for PD and related diseases.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

iNPH grading scale

Key secondary outcomes

3m up and go, Mini Mental Scale Examination, Frontary Assessment Battery,Trail making Tast, Wechsler Adult Intelligence Scale-Third Edition, Urinary drainage evaluation (urodynamics), Parkinsonnism (Dopa challenging test, MDS-Unified Parkinson's Disease Rating Scale part3)

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

No treatment

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

The randomly selected lumbar-abdominal shunt non-operative group will undergo surgery after 6 months from diagnosis.

Interventions/Control_2

The randomly selected lumbar-abdominal shunt surgery group will undergo surgery within 3 months of diagnosis.

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

60

years-old

<=

Age-upper limit

90

years-old

>

Gender

Male and Female

Key inclusion criteria

Patients who have any or all of the following symptoms: gait disturbance, cognitive dysfunction, or urinary dysfunction, and meet the criteria of Evans' index > 0.3, will undergo nuclear medicine examination (head MRI, DaT-SPECT, IMP-SPECT, MIBG myocardial scintigraphy).
Patients with disproportionately enlarged subarachnoid-space hydrocephalus (DESH) and gait disturbance should undergo CSF examination.
For patients with symptoms of gait disturbance but no DESH, a tap test is performed and cognitive function tests (MMSE: Mini Mental Scale Examination, FAB: Frontary Assessment Battery, WAIS-III: Trail Assessment Battery) are performed before and after (on the day of the tap test, 3 days later, and 7 days later), WAIS-III : Trail making Tast, Wechsler Adult Intelligence Scale-Third Edition), urinalysis (urodynamics), evaluation of parkinsonism (Dopa challenging test, MDS UPDRS partIII: MDS-Unified Parkinson's Disease Rating Scale partIII, iNPHGS: iNPH grading socre), and if symptoms improve, a diagnosis of normal pressure hydrocephalus is made.

Key exclusion criteria

Select patients with no pre-existing subarachnoid hemorrhage, meningitis, head trauma, congenital hydrocephalus, or aqueductal stenosis.If the CSF test shows CSF amyloid-beta42 < 500 pg/ml, CSF total tau > 600 pg/ml, and CSF phosphorylated tau > 60 pg/ml, the patient is likely to have Alzheimer's disease and should be excluded.

Target sample size

100

Name of lead principal investigator

1st name	Taiji
Middle name
Last name	Tsunemi

Organization

Juntendo University

Division name

Neurology

Zip code

113-8421

Address

2-1-1 Hongo, Bunkyo-ku, Tokyo

TEL

03-3813-3111

Email

t-tsunemi@juntendo.ac.jp

Name of contact person

1st name	Tomoyo
Middle name
Last name	Shimada

Organization

Juntendo University

Division name

Neurology

Zip code

113-8421

Address

2-1-1 Hongo, Bunkyo-ku, Tokyo

TEL

03-3813-3111

Homepage URL

Email

t-oyamada@juntendo.ac.jp

Institute

Juntendo University

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Hospital Ethics Committee Bureau, Soon Paradise Hospital, Soon Paradise University School of Medicine

Address

3-1-3 Hongo, Bunkyo-ku, Tokyo

Tel

03-5802-1584

Email

kenkyu5858@juntendo.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

順天堂大学順天堂医院

Date of disclosure of the study information

2023

Year

11

Month

26

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

Patients with iNPH + Parkinson's disease will be divided into two groups under the condition of random assignment: those who underwent lumbar-abdominal shunt surgery and those who did not undergo lumbar-abdominal shunt surgery.
All patients will undergo a gait test (3m up and go), cognitive function test (MMSE: Mini Mental Scale Examination, FAB: Frontary Assessment Battery, WAIS-III) before and after LPS surgery (at the same timing for the patients who did not undergo LPS surgery), urinary test (urodynamics), evaluation of parkinsonism (Dopa challenging test, MDS-Unified Parkinson's Disease Rating Scale partIII (MDS-UPDRS partIII), iNPHGS (iNPH grading socre)) at 3, 6 and 12 months after LPS surgery.
Patients will be assigned to the no LPS surgery group and will be considered for lumbar-abdominal shuntingLPS surgery at the 6-month follow-up evaluation or at any time during follow-up if their symptoms worsen. The specific criteria for determining whether a patient should undergo LPS surgery are a worsening of 5 points or more on the MDS-UPDRS part III, prolonged gait test(3m up and go) of 3 seconds or more, or obvious worsening of activities of daily living, or when the examiner or subject recognizes an obvious worsening of symptoms.
In addition, no changes in oral medications for Parkinson's disease are to be made during this trial.
All patients will undergo imaging re-evaluation with head MRI, DaT-SPECT, and IMP-SPECT at 12 months.

Adverse events

Outcome measures

Cognitive and mental status: MMSE, FAB, WAIS-III
Motor symptoms : 3m up and go, MDS-UPDRS partIII, iNPHGS score
Urinary : urodynamics

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2021

Year

05

Month

01

Day

Date of IRB

2021

Year

05

Month

21

Day

Anticipated trial start date

2021

Year

05

Month

22

Day

Last follow-up date

2025

Year

05

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2023

Year

11

Month

26

Day

Last modified on

2023

Year

11

Month

27

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000060361