Can extended treatment with N-pep-12 improve recovery after acute ischemic stroke?

ISRCTN ISRCTN15764675
DOI https://doi.org/10.1186/ISRCTN15764675
Secondary identifying numbers FSNN20200313
Submission date
15/04/2020
Registration date
29/04/2020
Last edited
19/11/2024
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Cognitive impairment is a common finding in patients with stroke, regardless of severity, with an important impact on the quality of life. Vascular cognitive impairment (VCI) describes a spectrum of cognitive disorders ranging from mild cognitive impairment (MCI) to dementia, with consequences for all cognitive domains and behaviour. This is a study to investigate the effects of N-Pep-12 treatment on the recovery of patients with post-stroke cognitive impairment. N-Pep-12 is a nutritional supplement that has been shown to have neuroprotective and pro-cognitive effects in experimental studies as well as in earlier clinical studies in patients suffering from age-related cognitive deficits.

Who can participate?
Adults aged 18 to 80 with supratentorial ischemic stroke onset 30-120 days before screening

What does the study involve?
Participants are randomly allocated to one of two groups. The first group take N-Pep-12 (90 mg) capsules, once per day, oral, for 360 days, while the second group do not receive any medication. Cognitive function is assessed after 0, 90 and 360 days.

What are the possible benefits and risks of participating?
The potential benefit of N-Pep-12 is improved cognitive function and brain recovery in patients with post-stroke cognitive impairment. The main risk for patients is developing adverse events, which are carefully assessed in order to establish a detailed safety profile of the intervention.

Where is the study run from?
RoNeuro Institute for Neurological Research and Diagnostic (Romania)

When has the study started and how long is it expected to run for?
April 2020 to October 2023

Who is funding the study?
The Society for the Study of Neuroprotection and Neuroplasticity (SSNN) (Romania)

Who is the main contact?
Stefan Strilciuc
stefan.strilciuc@ssnn.ro

Contact information

Prof Dafin Fior Muresanu
Scientific

No. 37 Mircea Eliade Street
Cluj-Napoca
400364
Romania

ORCiD logoORCID ID 0000-0002-9536-1153
Phone +40 (0)740066761
Email dafinm@ssnn.ro
Dr Olivia Verisezan Rosu
Public

No. 37 Mircea Eliade Street
Cluj-Napoca
400364
Romania

Phone +40 (0)744820493
Email olivia.rosu@ssnn.ro

Study information

Study designExploratory prospective randomized open-label controlled study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Other
Study typeTreatment
Participant information sheet No participant information sheet available
Scientific titleCombined neuropsychological, neurophysiological and psychophysiological assessment of the effects of N-Pep-12 on neurorecovery in patients after ischemic stroke - N-Pep-12 Extension
Study acronymN-Pep-12 Extension
Study objectivesThe study evaluates the therapeutic effect and the safety of a single daily dose of 90 mg of N-Pep-12 for 360 days in supporting neurorecovery in comparison to a control group of patients after ischemic stroke.
Ethics approval(s)Approved 27/03/2020, Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy (8 Babeş Street, 400012 Cluj-Napoca, Romania; +40 (0)264 597 256; contact@umfcluj.ro), ref: 115/16.03.2020
Health condition(s) or problem(s) studiedSupratentorial, radiologically confirmed ischemic stroke with the onset 30-120 days prior to screening
InterventionCurrent interventions as of 02/06/2020:
The study is organised into three visits:
Visit 1 – Screening / Baseline - Study Day 0
Visit 2 – Efficacy / Safety - Study Day 90
Visit 3 – Efficacy / Safety - Study Day 360

No follow-up will be performed after the 360-day evaluation.

The study arms will be administered the following treatment courses:
1. Treatment Group: N-Pep-12 (90 mg) capsules 1/ day oral for 360 days
2. Reference Group: will not receive any kind of medication or placebo

Randomisation, Blinding and Unblinding
This is an open-label study. Communication is forbidden between assessments and the person who gives the treatment.
Patients who meet the inclusion and exclusion criteria will be randomly assigned to the treatment group or control group, in a 2:1 ratio.


Previous interventions:
The study is organised into three visits:
Visit 1 – Screening / Baseline - Study Day 0
Visit 2 – Efficacy / Safety - Study Day 90
Visit 3 – Efficacy / Safety - Study Day 360

No follow-up will be performed after the 360-day evaluation.

The study arms will be administered the following treatment courses:
1. Treatment Group: N-Pep-12 (90 mg) capsules 1/ day oral for 360 days
2. Reference Group: will not receive any kind of medication or placebo

Randomisation, Blinding and Unblinding
This is a single-blinded study. Communication is forbidden between assessments and the person who gives the treatment.
Patients meeting the inclusion and exclusion criteria will be randomly assigned to receive active treatment based on the time of their enrollment in the study. Randomisation was performed 2:1 (2 -intervention, 1 -control). The first two patients enrolled will receive active treatment, the third patient will be in the control group. This allocation scheme shall be continued until 90 patients have been enrolled.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase IV
Drug / device / biological / vaccine name(s)N-Pep-12
Primary outcome measure1. Cognitive function assessed using Montreal Cognitive Assessment (MoCA) at days 0, 90, 360
2. Emotional status assessed using Hospital Anxiety and Depression Scale at days 0, 90, 360
3. Cognitive function assessed using Digit Span (Wechsler adult intelligence scale – third edition at days 0, 90, 360
4. Cognitive function assessed using Color Trails Test at days 0, 90, 360
5. Cognitive function assessed using PSI (Processing Speed Index, Wechsler adult intelligence scale – third edition) at days 0, 90, 360
Secondary outcome measures1. Safety variables:
1.1. Adverse events/serious adverse events measured using a questionnaire at 90 and 360 days
1.2. Mortality reported at any time during the study
2. Subgroup analysis:
2.1. Eye movements assessed using a Tobii Pro TX300 eye tracking device and analyzed using Tobii Studio software at days 0, 90, 360
2.2. Brain electrical activity assessed using electroencephalography (EEG) and analyzed quantitatively using BrainAnalyzer software at days 0, 90, 360
Overall study start date13/03/2020
Completion date31/10/2023

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit80 Years
SexBoth
Target number of participants90
Total final enrolment107
Key inclusion criteria1. Stroke onset 30-120 days prior to screening
2. Stroke is ischemic in origin, supratentorial, and radiologically confirmed (CT or MRI)
3. No significant pre-stroke disability (pre-stroke Modified Rankin Score of 0 or 1)
4. Goodglass and Kaplan Communication Scale Score of > 2 at screening
5. No other radiologically confirmed stroke in the 3 months preceding index stroke
6. Age between 18 and 80 years, inclusive
7. Signed informed consent form
Key exclusion criteria1. Pre-existing and active major neurological disease
2. Pre-existing and active (e.g., on chronic medication) major psychiatric disease, such as major depression, schizophrenia, bipolar disease, or dementia (the short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score >3)
3. Advanced liver, kidney, cardiac, or pulmonary disease
4. A terminal medical diagnosis consistent with survival < 1 year
5. Major drug dependency, including alcohol (in the investigator’s judgment)
6. Injury of writing hand influencing cognitive or other outcome measures, in the investigator’s judgment
7. Females who are pregnant or lactating
Date of first enrolment30/04/2020
Date of final enrolment31/10/2022

Locations

Countries of recruitment

  • Romania

Study participating centre

RoNeuro Institute for Neurological Research and Diagnostic
37 Mircea Eliade Street
Cluj-Napoca
400364
Romania

Sponsor information

The Foundation for the Study of Neuroscience and Neuroregeneration (Fundatia pentru Studiul Nanoneurostiintelor si Neuroregenerarii)
Research organisation

No. 37 Mircea Eliade Street
Cluj-Napoca
400364
Romania

Phone +40 (0)740150076
Email office@ssnn.ro

Funders

Funder type

Research organisation

The Foundation for the Study of Neuroscience and Neuroregeneration (Fundatia pentru Studiul Nanoneurostiintelor si Neuroregenerarii)

No information available

Results and Publications

Intention to publish date31/12/2024
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal. Additional documents will be made available at a later date.
IPD sharing planThe datasets generated during and/or analysed during the current study are/will be available upon request

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol file version 3.0 13/03/2020 20/10/2023 No No
Results article 28/09/2024 19/11/2024 Yes No

Additional files

ISRCTN15764675_Protocol_v3.0_13March2020.pdf

Editorial Notes

19/11/2024: Publication reference added.
20/10/2023: The protocol (not peer reviewed) was uploaded.
22/05/2023: The following changes were made to the study record:
1. The recruitment end date was changed from 31/05/2023 to 31/10/2022.
2. The overall study end date was changed from 31/05/2024 to 31/10/2023.
3. Total final enrolment and IPD sharing statement added.
02/06/2020: The interventions have been updated.
16/04/2020: Trial's existence confirmed by Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy.