Examination of a potential inflammatory response in the blood of individuals with ALSP and the effect of a stem cell transplant on this inflammatory response

ISRCTN	ISRCTN31547763
DOI	https://doi.org/10.1186/ISRCTN31547763
Secondary identifying numbers	NL74275.029.20

Submission date: 27/07/2022
Registration date: 09/08/2022
Last edited: 05/08/2022

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
The brain consists of gray matter and white matter. The white matter ensures the transmission of information to other brain areas and to the rest of the body. In individuals with the disease “Adult-onset Leukoencephalopathy with axonal Spheroids and Pigmented glia (ALSP)”, the white matter in the brain is damaged, leading to disrupted transmission of information. As a result, various complaints can arise, for example problems with memory or with walking. The damage to the brain is (partly) caused by diseased 'microglia'. Microglia are immune cells that remove harmful material from the brain. In ALSP patients, the microglia become diseased and disappear due to an error in the DNA. As a result, harmful material in the brain can no longer be properly cleaned up. In addition, the brain damage may trigger an inflammatory response in the body which is visible in the blood.
Early in the disease, the diseased microglia can be replaced with healthy microglia from a donor. This is done through a stem cell transplant, also known as a bone marrow transplant. The healthy donor microglia can properly clean up the harmful material in the brain. In this way new damage to the brain is prevented. Research in other white matter diseases shows that the healthy donor microglia also reduce the inflammatory response in the body. The aim of this study is therefore to investigate the presence of the inflammatory response in the body in individuals with ALSP by examination of their blood and to study whether a stem cell transplant reduces the inflammatory response. The results of this study may contribute to improved treatment of ALSP.

Who can participate?
All individuals with ALSP in whom the error in the DNA causing ALSP has been identified and are referred to the Amsterdam UMC, location VUmc or AMC and are considered to be eligible for stem cell transplant.

What does the study involve?
We want to take approximately fifteen milliliters of extra blood from subjects participating in this study over a period of five years during six regular blood draws. Regular blood draws take place as part of standard care for individuals with ALSP.

What are the possible benefits and risks of participating?
There is no direct benefit for the patients; there is only benefit for the ALSP patient population by increased knowledge. Risks and burdens of the study will be minimized by collecting blood samples only during venous blood sampling in the context of standard care.

Where is the study run from?
Amsterdam UMC (Netherlands)

When is the study starting and how long is it expected to run for?
July 2020 to July 2030

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Shanice Beerepoot, s.beerepoot@amsterdamumc.nl

Study website

Contact information

Mrs Shanice Beerepoot
Scientific

De Boelelaan 1118
Amsterdam
1081 HV
Netherlands

ORCID ID	0000-0003-2945-6784
Phone	+31-20-4441035
Email	s.beerepoot@amsterdamumc.nl

Study information

Study design	Longitudinal cohort study
Primary study design	Observational
Secondary study design	Cohort study
Study setting(s)	Hospital
Study type	Other
Participant information sheet	No participant information sheet available
Scientific title	Systemic inflammation in ALSP patients and the effect of an allogenic hematopoietic stem cell transplantation on the inflammation
Study acronym	ALSP-INFLAM
Study objectives	1. Cytokine profiles in blood of untreated patients with ALSP differ from cytokine profiles in blood of healthy individuals, revealing an increased production of proinflammatory cytokines 2. Treatment with an allogeneic hematopoietic stem cell transplantation decreases the levels of proinflammatory cytokines, reducing systemic inflammation in treated patients with ALSP over time
Ethics approval(s)	Approved 16/12/2020, Amsterdam UMC VUmc site Ethics Committee (De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; +31 20 444 4444; metc@vumc.nl), ref: 2020.374
Health condition(s) or problem(s) studied	Observational study in untreated and treated patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)
Intervention	The procedure includes collection of ±15ml extra venous blood at the moment of venous blood sampling for standard clinical care during a period of 5 years (6 times in total). Primary analyses of plasma cytokines will be done by using a high-throughput, multiplex immunoassay.
Intervention type	Other
Primary outcome measure	Cytokine profiles in blood before/without treatment, expressed in Normalized Protein eXpression (NPX) in Log2 scale, and cytokine profiles in blood over time (6 times over 5 years)
Secondary outcome measures	Clinical outcomes after treatment measured using patient records 1. Modified Rankin Scale score 2. Guys Neurological Disability score 3. Health Utilities Index score 4. Cognitive function 5. Total HDLS MRI score
Overall study start date	01/07/2020
Completion date	01/07/2030

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	15
Key inclusion criteria	1. Diagnosis of ALSP confirmed by a pathogenic CSF1R mutation 2. Aged 18 years or older 3. Capable of giving informed consent
Key exclusion criteria	1. No informed consent given by the patient 2. Cognitive capabilities are too low at inclusion of the study to give informed consent
Date of first enrolment	03/02/2022
Date of final enrolment	01/07/2025

Locations

Countries of recruitment

Netherlands

Study participating centres

Amsterdam UMC, VUmc site

De Boelelaan 1118
Amsterdam
1081 HV
Netherlands

Amsterdam UMC, AMC site

Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Sponsor information

Amsterdam UMC Location VUmc
Hospital/treatment centre

De Boelelaan 1118
Amsterdam
1081 HV
Netherlands

Phone	+31-20-5667508
Email	n.wolf@amsterdamumc.nl
Website	http://www.vumc.nl/
"ROR"	https://ror.org/00q6h8f30

Funders

Funder type

Other

Investigator initiated and funded

No information available

Results and Publications

Intention to publish date	01/07/2031
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a high-impact peer-reviewed journal
IPD sharing plan	Unpublished anonymized data will be available on reasonable request from a qualified investigator after publication of the primary and secondary outcomes of this study

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol file	version 5	17/02/2022	29/07/2022	No	No

Additional files

42135 Protocol v5 17Feb2022.pdf

Editorial Notes

29/07/2022: Trial's existence confirmed by VUMC