Cognitive brain circuits and the spread of tau in vivo in humans

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

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

18 May 2018 → ongoing

Decision date (initial)

2024-08-27

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

FWO (grant #G094418N), Bijzonder Onderzoeksfonds KU Leuven C14/21/109

External identifiers

EU CT number

2024-511613-38-01

EudraCT number

2018-001257-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To determine how the spread of tau aggregates in the different phases of Alzheimer disease (AD) (the preclinical, the prodromal, and the early dementia phase) affects the functional organization of the language circuit.

Secondary objectives 1

1. To determine the topographical spread of tau across different stages (the preclinical, the prodromal and the early dementia stage) of Alzheimer disease

Conditions and MedDRA coding

Alzheimer disease in a preclinical and prodromal stage

Regulatory references

Plan to share IPD

Yes

IPD plan description

The de-identified individual data obtained during this research can be utilized for other research projects regarding Alzheimer disease or related disorders but only conditional on approval by the PI Rik Vandenberghe and by the Ethics Committee Clinical Studies UZ/KU Leuven. Under these conditions the deidentified individual research data can be shared with other research partners within KU Leuven or other scientific institutions involved in research on Alzheimer disease and related disorders. If the research results lead to publication, the publication will contain a data sharing statement. The data that can be shared are: the individual participant data that underlie the results reported in the article, after deidentification (text, tables, figures and appendices) and the study protocol. Data sharing will be through the KU Leuven repository. Proposals should be directed to the PI. To gain access, data requestors will need to sign a data access agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 40 patients with mild to moderate clinically probable AD according to the National Institute of Aging (NIA)-Alzheimer's Association (AA) diagnostic criteria [22], and an MMSE of 16 or higher and a Clinical Dementia Rating scale total score of 0.5 or 1.
2. 40 patients with amnestic MCI due to AD according to the NIA-AA diagnostic criteria [3], an MMSE 25 or higher, and a Clinical Dementia Rating scale total score of 0.5.
3. 40 amyloid-positive cognitively intact healthy controls, recruited via a longitudinal community-recruited cohort that is followed at the Laboratory for Cognitive Neurology (see below) (mean age = 68.4 6.4, range 55-80 years).
4. 40 matched amyloid-negative cognitively intact healthy controls. These subjects will be matched in age, education and gender to the three first cohorts.

Exclusion criteria 6

1. Patients who are unable to provide written informed consent
2. Participants with significant medical, neurological or psychiatric comorbidity
3. Structural lesions on MRI, such as large-vessel strokes, sequellae of macrohemorrhages, arachnoidal cysts, and posttraumatic lesions, will be an exclusion criterion. White matter lesions will be allowed.
4. Women of childbearing potential. Female subjects who are of childbearing potential are eligible to participate if they use a highly effective method of contraception that is either user-dependent (combined (estrogen- and progestogen-containing) hormonal contraception or progestogen-only hormonal contraception associated with inhibition of ovulation) or user-independent (implantable progestogen-only hormonal contraception associated with inhibition of ovulation), vasectomized partner or sexual abstinence). Female subjects are not considered of childbearing potential if they are surgically sterile (hysterectomy or bilateral salpingectomy/oophorectomy), or postmenopausal for at least 1 year prior to screening (defined as no menses for more than 12 months without an alternative medical cause).
5. Female partner of male subjects must be surgically sterile (hysterectomy or bilateral salpingectomy/oophorectomy or bilateral tubal occlusion/ligation) or postmenopausal for at least 1 year prior to screening.
6. Individuals with a history of epilepsy or a known family history of epilepsy will be excluded from the 40 Hz stimulation paradigm

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Effect of tau aggregates on activity amplitude in the perisylvian network 2. Effect of tau aggregates on functional connectivity measures

Secondary endpoints 1

1. Effect of tau aggregates on EEG based measures of functional connectivity

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Rik Vandenberghe

Public contact point

Organisation

UZ Leuven

Contact name

Rik Vandenberghe

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 6 files

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

Application history

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