A Randomized Cross-over Study for Normal Pressure Hydrocephalus (ARCS NPH)

Efficacy of Shunt Surgery in Normal Pressure Hydrocephalus: a Randomized Cross-over Study

The goal of our study is to verify the effectiveness of the shunt and to identify the most sensitive criteria to select patients for surgery. The study is designed to assess improvement in walking and balance (gait), urinary function and memory after shunting. In addition, the study aims to identify the most accurate and sensitive tools to measure improvement for our patients.

Study Overview

• Status: Completed
• Conditions: Normal Pressure Hydrocephalus
• Intervention / Treatment: Device: MIETHKE proGAV® / MIETHKE proSA®

Detailed Description

Normal Pressure Hydrocephalus (NPH) causes memory loss, walking, and urinary difficulties. If NPH goes unidentified and untreated it can cause severe disability. The cause of this disease is poorly understood. It may involve damage caused by impaired blood flow in the brain.

The standard methods by which we diagnose patients who have symptoms of NPH are less accurate than desired. Many times patients remain undiagnosed or untreated while others receive treatment due to a false-positive diagnosis.

To treat NPH, a small tube called a 'shunt' can be surgically placed in the brain to drain cerebrospinal fluid (CSF) and help relieve symptoms. Currently, the reported response rates to shunting vary from 31% to 89%. Follow-up studies have shown that the shunts may not work long-term. This could be due to the natural history of the disease, development of other diseases, or due to a short term 'placebo effect' following the shunt placement surgery.

Our group is doing a study of patients with NPH. All participants in this study will have a shunt placed. These shunts are programmable and, once placed, may be opened or closed by the doctor. Programming the shunt does not require an additional surgical procedure. All study participants will be divided into two groups. One group will have their shunts open and draining. The other group will have their shunts closed (not draining). After 6 weeks, the groups will be switched. Those with open shunts will have them closed, and the group with closed, non-draining shunts, will have theirs opened. Participants will not know if their shunts are open (draining) or if they are closed (not draining). Study participants will be followed for two years. Any participants who develop recurrent, new or worsening symptoms will be taken off study and treated according to good medical practice.

The purpose of this study is to (a) look for symptom improvement in response to the draining shunt compared to the non-draining shunt (placebo affect), (b) find 'predictors' that will help doctors identify patients who will respond well to shunt placement, (c) monitor the long-term effects of these shunts, and (d) assess current diagnostic testing to see which methods are most accurate.

Eligibility Criteria:

Inclusion Criteria

1. Age of Patients ( between 60 to 85 years old).
2. Clinically suspected Idiopathic Normal Pressure Hydrocephalus (iNPH) with at least gait impairment.
3. Informed consent from patient.

Exclusion Criteria

1. Etiology for hydrocephalus other than iNPH.
2. Patients not capable of providing an informed consent.
3. History of intra-cerebral hemorrhage.
4. Cardiac Pacemaker.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21284
      • Johns Hopkins University
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Virginia
    • Richmond, Virginia, United States, 23220
      • Virgina Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age of Patients ( between 60 to 85 years old)
• Clinically suspected Normal Pressure Hydrocephalus (NPH) with at least gait impairment
• Informed consent from patient

Exclusion Criteria:

• Etiology for hydrocephalus other than idiopathic normal pressure hydrocephalus
• Patients not capable of providing an informed consent.
• History of intra-cerebral hemorrhage
• Cardiac Pacemaker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Shunt; The programmable valve, MIETHKE proGAV® / MIETHKE proSA®, will be open at this time. The adjustment is done in the out-patient clinic.	Device: MIETHKE proGAV® / MIETHKE proSA®; The programmable shunt will be adjusted through the MIETHKE proGAV® / MIETHKE proSA® valve and crossed over at 6 weeks. The open shunt will be adjusted to be closed. The closed shunt will be adjusted to open.
Placebo Comparator: Closed Shunt; The programmable valve, MIETHKE proGAV® / MIETHKE proSA®, will be closed during this time. The adjustment is done in the out-patient clinic.	Device: MIETHKE proGAV® / MIETHKE proSA®; The programmable shunt will be adjusted through the MIETHKE proGAV® / MIETHKE proSA® valve and crossed over at 6 weeks. The open shunt will be adjusted to be closed. The closed shunt will be adjusted to open.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tinetti Score on Open Shunt vs. Closed Shunt	The Tinetti tool test measures walking and balance. It is designed to determine an elders risk for falls within the next year. It takes about 8-10 minutes to complete. The patient is asked to complete the gait portion first with the evaluator walking close behind the elder and evaluating gait steppage and drift. The patient is then asked to complete the balance portion with the evaluator again standing close by the patient (towards the right and in front). The patient is then asked to sit and the score is then totaled.The higher the score, the better the performance. Scoring is done on a three point scale with a range on each item of 0-2 with 0 representing the most impairment. Individual scores are then combined to form three scales: a Gait Scale, a Balance Scale and then and overall Gait and Balance score. The maximum score for gait is 12 points while the maximum for Balance is 16 points with a total maximum for the overall score of 28 points.	6 weeks
Timed Up and Go (TUG) Score on Open Shunt vs. Closed Shunt	The TUG evaluation measures walking and balance. The patient is timed while they rise from an arm chair (approximate seat height 46 cm), walk at a comfortable and safe pace to a line on the floor three meters away, turn and walk back to the chair and sit down again. The patient walks through the test once before being timed to become familiar with the test. The subject wears his regular footwear and uses a walking aid (cane or walker) if necessary. A faster time indicates a better functional performance and a score of ≥13.5 seconds is used as a cut-point to identify those at increased risk of falls.	6 weeks
Medical College of Virginia (MCV) Gait Grade on Open Shunt vs. Closed Shunt	The MCV gait grade evaluation measures balance and walking. The score ranges from 1 to 6 with higher values suggesting worse gait performance.	6 weeks
Kiefer Score on Open Shunt vs. Closed Shunt	The Kiefer is a modified clinical grading tool that measures the severity of the three key symptoms (mental deficits, gait disturbance, incontinence) and two additional minor symptoms (headache and dizziness). The overall score may reach values between 0 and 24, with higher scores indicating more severe impairment	6 weeks
Kubo Score on Open Shunt vs. Closed Shunt	The Kubo tool measures your symptoms in three categories: cognitive (attention and memory), gait/balance and urinary function.The score ranges from 0 to 24 with higher scores indicating worse symptoms	6 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Ohio State University; Henry Ford Health System; Rhode Island Hospital; Virginia Commonwealth University; Aesculap, Inc.
• Investigators: Principal Investigator: Daniele Rigamonti, MD FACS, Johns Hopkins University; Study Director: Jennifer Lu, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): September 14, 2017
• Study Completion (Actual): September 14, 2017

Study Registration Dates

• First Submitted: January 31, 2013
• First Submitted That Met QC Criteria: February 22, 2013
• First Posted (Estimate): February 26, 2013

Study Record Updates

• Last Update Posted (Actual): November 2, 2018
• Last Update Submitted That Met QC Criteria: October 31, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Hydrocephalus; Cross-over
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: NA_00042178