Plasma Dilution and Infusion to Improve Cognition in Mild Cognitive Impairment (MCI) (ADDITION-MCI)

In the ADDITION-MCI project, patients with a diagnosis of mild cognitive impairment probably caused by Alzheimer's disease will receive plasma exchange.

Study Overview

• Status: Enrolling by invitation
• Conditions: Alzheimer Disease
• Intervention / Treatment: Biological: Plasma exchenge

Detailed Description

Repeated plasma exchanges will be conducted, and cognitive outcomes will be measured before and after the intervention.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0450
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Clinical diagnosis of Alzheimer's Disease

MoCA score < 27 and >17

Able to give informed consent as judged by the doctor setting the AD diagnosis and study doctor.

At least one biomarker of the AT(N)-classification system supporting the diagnosis

Expected to live more than five years at inclusion by the study doctor.

Exclusion Criteria:

Known IgA deficiency

Known severe protein S depletion

Previous severe allergic reaction after transfusion of a blood product

Known heart failure

Known liver failure

Known kidney failure

Previous cancer <10 years.

Not deemed able to participate by the study staff

Other severe chronic diseases, interfering with the TPE-procedure

Ongoing infections

Other unresolved medical conditions

Known coagulopathies

Fulfilling ICD-10 criteria for dementia at baseline, as evaluated by the evaluating physician.

Peripheral veins not expected to be suitable for repeated venous access procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plasma exchange; 1-20 plasma exchanges.	Biological: Plasma exchenge; Plasma exchange will be conducted. The substitution fluid will be plasma from ha healthy donor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Safety of the intervention in the patient group measured as number and severity of adverse events. This will be evaluated as the number of participants with treatment-related adverse events as assessed by CTCAE v5.0.	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montreal Cognitive Assessment (MoCA) Test for Dementia	Change from baseline to after completion of all procedure cycles	2 months
Change in Montreal Cognitive Assessment (MoCA) Test for Dementia	Change from baseline to after the procedure	6 months
Change in Montreal Cognitive Assessment (MoCA) Test for Dementia	Change from baseline to after the procedure	12 months
Change in Montreal Cognitive Assessment (MoCA) Test for Dementia	Change from baseline to after the procedure	24 months
Change in Montreal Cognitive Assessment (MoCA) Test for Dementia	Change from baseline to after the procedure	48 months
Burden of participation questionnaire sum score	At the end of the procedure	2 months
Change in IL10 from baseline	Change in IL10	2 months
Change in IL10 from baseline	Change in IL10	6 months
Change in IL6 from baseline	Change in IL6	2 months
Change in IL6 from baseline	Change in IL6	6 months
Change in grip strength from baseline	Change in grip strength from baseline	2 months
Change in grip strength from baseline	Change in grip strength from baseline	6 months
Change in grip strength from baseline	Change in grip strength from baseline	12 months
Change in grip strength from baseline	Change in grip strength from baseline	24 months
Change in grip strength from baseline	Change in grip strength from baseline	48 months
Change in the CERAD 10-word test performance from baseline	Change in the CERAD 10-word test performance from baseline	2 months
Change in the CERAD 10-word test performance from baseline	Change in the CERAD 10-word test performance from baseline	6 months
Change in the CERAD 10-word test performance from baseline	Change in the CERAD 10-word test performance from baseline	12 months
Change in the CERAD 10-word test performance from baseline	Change in the CERAD 10-word test performance from baseline	24 months
Change in the CERAD 10-word test performance from baseline	Change in the CERAD 10-word test performance from baseline	48 months
Change in the trail making test A or B (as appropriate) time from baseline	Change in the trail making test A or B (as appropriate) time from baseline	2 months
Change in the trail making test A or B (as appropriate) time from baseline	Change in the trail making test A or B (as appropriate) time from baseline	6 months
Change in the trail making test A or B (as appropriate) time from baseline	Change in the trail making test A or B (as appropriate) time from baseline	12 months
Change in the trail making test A or B (as appropriate) time from baseline	Change in the trail making test A or B (as appropriate) time from baseline	24 months
Change in the trail making test A or B (as appropriate) time from baseline	Change in the trail making test A or B (as appropriate) time from baseline	48 months
Change in IQCODE from baseline	Measured at the nearest next-of-kin	2 months
Change in IQCODE from baseline	Measured at the nearest next-of-kin	6 months
Change in IQCODE from baseline	Measured at the nearest next-of-kin	12 months
Change in IQCODE from baseline	Measured at the nearest next-of-kin	24 months
Change in IQCODE from baseline	Measured at the nearest next-of-kin	48 months
Change in 4 meter walk test from baseline		2 months
Change in 4 meter walk test from baseline		6 months
Change in 4 meter walk test from baseline		12 months
Change in 4 meter walk test from baseline		24 months
Change in 4 meter walk test from baseline		48 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in DNA methylation age GrimAge2 from baseline	Epigenetic measurement	6 months
Proteomic profile	Comparison of the proteomic profile at baseline and the proteomic profile at 12 months. The profile will be measured using SomaLogic assays and in this endpoint the concentration of each protein at baseline will be compared to the concentration at 12 months.	12 months
Single cell RNA seq		6 months
Change in EQ5D	The EQ5D questionnaire will be used	12 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Vestre Viken Hospital Trust; Nasjonalforeningen for folkehelsen; Impetus Grants (EIN: 87-1540960)

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: January 22, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: 520697

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will attempt to share IDP within the European GDPR rules.
• IPD Sharing Time Frame: Before data analysis and publication
• IPD Sharing Access Criteria: On request to the study contact.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No