MRI contrast agent in the spinal canal to investigate transportation of the cerebrospinal fluid in the brain.

2024-520146-33-00 Phase I and Phase II (Integrated) - Other Ongoing, recruiting

Start 13 Jan 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - Other
Status Ongoing, recruiting
Participants planned 60
Countries 1
Sites 1

Cerebrospinal fluid circulation disorder seen in clinically suspected idiopathic normal pressure hydrocephalus, Alzheimers Disease and healthy controls.

To quantify the distribution and rate of elimination of the contrast agent as assessed by repeated MRI in humans. We will also document any adverse events related to the administration of Gadovist

Key facts

Sponsor
Region Vaesterbotten
Participant type
Patients, Healthy volunteers
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Trial duration
13 Jan 2025 → ongoing
Decision date (initial)
2025-01-13
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Region Västerbotten (ALF‑medel) · Alzheimerfonden · Stiftelsen för strategisk forskning · Vetenskapsrådet

External identifiers

EU CT number
2024-520146-33-00
EudraCT number
2020-005542-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

To quantify the distribution and rate of elimination of the contrast agent as assessed by repeated MRI in humans. We will also document any adverse events related to the administration of Gadovist

Secondary objectives 3

  1. To investigate the driving mechanism of the flow and if the quantified glymphatic function can be used to predict which INPH patients that will be improved by shunting with CSF shunt
  2. Determine if there is a difference in quantified glymphatic function between INPH, AD and HC and examine how CSF flow metrics associate with disease-specific biomarkers such as beta amyloid concentration in brain tissue and in cerebrospinal fluid.
  3. Investigate if CSF flow metrics is predictive of the degree of cognitive impairment and progression in AD.

Conditions and MedDRA coding

Cerebrospinal fluid circulation disorder seen in clinically suspected idiopathic normal pressure hydrocephalus, Alzheimers Disease and healthy controls.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

  1. Patients investigated for suspected idiopathic normal pressure hydrocephalus at Umeå University hospital
  2. Patients with Alzheimers disease.
  3. Healthy controls

Exclusion criteria 11

  1. Age <65 for INPH. Age <55 years for AD and HC
  2. Not able to understand instructions needed for informed concent
  3. known contradicting allergies
  4. Known contraindications for magnetic reconance imaging
  5. Renal impairment (as deffined by blood test at admission)
  6. Current treatment with anticoagulation medication
  7. Low threshold for seizures
  8. History of bronchial asthma
  9. Previous investigation with gadolinium contrast medium
  10. Mini mental state examination (MMSE) < 20
  11. Liver failure

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. Time-dependent change in signal intensity on brain MRI after intrathecal contrast administration will be analyzed with indicator dilution algorthim that will be optimized using computational fluid dynamic simulations.
  2. Registration of possible adverse events related to the intrathecal injection of Gadovist

Secondary endpoints 3

  1. Comparision between the distribution of the contrast and other MRI-sequences and cerebrospinal fluid dynamic parameters which provides us with information regarding possible driving mechanisms for the distribution.
  2. Quantified pre-operative glymphatic function will be correlated to clinical improvment after CSF shunting of INPH patients
  3. Quantified pre-operative glymphatic function will be correlated to clinical progress and beta-amyloid content in HC and AD-patients.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Gadovist 1.0 mmol/ml solution for injection

PRD377690 · Product

Active substance
Gadobutrol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRATHECAL USE
Authorisation status
Authorised
ATC code
V08CA09 — GADOBUTROL
Marketing authorisation
PL 00010/0535
MA holder
BAYER PLC
MA country
XI
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Auxiliary 1

VIZAMYL 400 MBq/mL solution for injection

PRD10888598 · Product

Active substance
Flutemetamol (18F)
Substance synonyms
Flutemetamol F 18, FLUTEMETAMOL F-18
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENUS USE
Authorisation status
Authorised
ATC code
V09AX04 — -
Marketing authorisation
EU/1/14/941/001
MA holder
GE HEALTHCARE AS
MA country
Liechtenstein
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Vaesterbotten

Sponsor organisation
Region Vaesterbotten
Address
Koksvagen 11, Alidhem Alidhem
City
Umea
Postcode
907 37
Country
Sweden

Scientific contact point

Organisation
Region Vaesterbotten
Contact name
Prof Malm, Department of neurology

Public contact point

Organisation
Region Vaesterbotten
Contact name
Prof Malm, Department of neurology

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Sweden Ongoing, recruiting 60 1
Rest of world 0

Investigational sites

Sweden

1 site · Ongoing, recruiting
Region Vaesterbotten
Neurology, Umea University, 901 85, Umea

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Sweden 2025-01-13 2025-01-13

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) 03 Provningsprotokoll 20260520 4
Recruitment arrangements (for publication) Mandatory field 1
Subject information and informed consent form (for publication) Bilaga 5 Patientinformation orginal 211013 1
Summary of Product Characteristics (SmPC) (for publication) 07 SmPC Gadobutrol Gadovist 1
Synopsis of the protocol (for publication) 04 Synopsis 260326 2

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-12-17 Sweden Acceptable
2025-01-13
2025-01-13
2 SUBSTANTIAL MODIFICATION SM-2 2026-03-25 Sweden Acceptable
2026-06-01
2026-06-01