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Salicornia for Neurovascular Health Improve

Primary Purpose

Stroke, Ischemic Stroke, Neurovascular Injury

Status
Recruiting
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Food supplement based on Salicornia extracts
Placebo
Sponsored by
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Stroke focused on measuring Polyphenol, Salicornia, Brain ischemia, Neuroprotection, Halophytes

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Substudy A: Inclusion Criteria: Patients ≥18 years old Possibility of analytical controls at the beginning/end of the study. Willingness and ability to give informed consent. Exclusion Criteria: Known neurovascular disease. Other chronic diseases for which the subject is taking medication on a regular basis. Hyperthyroidism according to the investigator's criteria. Volunteers taking vitamin or polyphenol-containing nutritional supplements in the 30 days prior to the screening visit (at the investigator's discretion). Severe illness with life expectancy of less than three months. Known allergies or intolerance to halophyte plants. Pregnant or lactating women. Presence of active neoplastic disease. Having participated in another clinical trial with medicinal products in the 30 days prior to the screening visit, or intending to do so during their participation in this study. Habitual consumption of halophyte plants. Patients who, at the investigator's discretion, are not able to comply with the study protocol. Substudy B: Inclusion criteria: Patients ≥18 years old. Patients with typical symptoms lasting less than 24 hours seen at the HUVM classified as TIA or minor stroke (if Diffusion weighted imaging (DWI) positive on magnetic resonance imaging (MRI)) during the last year. Have a neuroimaging performed at the time of the acute episode that rules out other non-vascular lesions. Willingness and ability to give informed consent. Exclusion criteria: Patients taking vitamin or polyphenol-containing nutritional supplements in the 30 days prior to the screening visit (at the investigator's discretion). Having participated in another clinical trial with medicinal products in the 30 days prior to the screening visit, or intending to do so during their participation in this study. Hyperthyroidism at the investigator's discretion. Dysphagia that prevents the intake of the study treatment. Patients dependent for basic activities of daily living (mRS >3) or with severe disease with life expectancy of less than 12 months. Known allergies or intolerance to halophyte plants. Habitual consumption of halophyte plants. Pregnant or lactating women. Presence of active neoplastic disease. Patients who, at the investigator's discretion, are unable to comply with the study protocol. Substudy C: Inclusion criteria: Patients ≥18 years of age. Lacunar syndrome with acute ischaemic lesion on neuroimaging of less than 1.5 cm maximum diameter. Willingness and ability to give informed consent. Exclusion criteria: Patients taking vitamin or polyphenol-containing nutritional supplements in the 30 days prior to the screening visit (at the investigator's discretion). Hyperthyroidism at the investigator's discretion. Claustrophobia or morbid obesity (IMT >40) precluding performance of MRI 3 Tesla. Patients dependent for basic activities of daily living (mRS >3) or with severe disease with an expected life expectancy of less than 12 months. Dysphagia that prevents the intake of the study treatment. Known allergies or intolerances to halophyte plants. Pregnant or breastfeeding women. Presence of active neoplastic disease. Having participated in another clinical trial with medicinal products in the 30 days prior to the screening visit, or intending to do so during their participation in this study. Habitual consumption of halophyte plants. Patients who, at the investigator's discretion, are not able to comply with the study protocol. Substudy D: Inclusion criteria: Patient with carotid stenosis that warrants treatment in one of the following cases: Symptomatic carotid stenosis >50% with stroke within 6 months prior to inclusion and not disabling at the time of inclusion. Asymptomatic carotid stenosis >70% provided some of the following criteria are met: I. Presence of silent stroke on neuroimaging. II. Stenosis with progression (>20%). III. Soft or ulcerated (unstable) plaque. IV. Occlusion of contralateral internal carotid artery (ICA). V. Impaired haemodynamic reserve. Receive carotid angioplasty and stenting (CAS) of said artery within a maximum of one month after inclusion and with a minimum of one week of taking the treatment from inclusion to intervention. Be able to orally take the dietary supplement/placebo from the event until just prior to the intervention. Patients ≥18 years. Willingness and ability to give informed consent. Exclusion criteria: Patients taking vitamin or polyphenol-containing nutritional supplements in the 30 days prior to the screening visit (at the investigator's discretion). Hyperthyroidism at the investigator's discretion. Claustrophobia or morbid obesity preventing the performance of MRI 1.5 Tesla. Severe disease with expected life expectancy of less than one month. Dysphagia preventing the intake of the study treatment. Known allergies or intolerance to halophyte plants. Pregnant or lactating women. Presence of active neoplastic disease. Having participated in another clinical trial with medicinal products in the 30 days prior to the screening visit, or intending to do so during their participation in this study. Habitual consumption of halophyte plants. Patients who, at the investigator's discretion, are not able to comply with the study protocol.

Sites / Locations

  • Hospital Universitario Virgen MacarenaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Food supplement based on Salicornia extracts

Placebo

Arm Description

Participants will receive food supplement based on halophyte plant (Salicornia) extracts, 1 g (two 0.5 gram capsules) orally once a day for a treatment period of 3 months (substudy A), 11 months (substudy B), 1 year (substudy C) or 7-30 days (substudy D).

Participants will receive two capsules once a day of placebo physically equal to the nutritional supplement for a treatment period of 3 months (substudy A), 11 months (substudy B), 1 year (substudy C) or 7-30 days (substudy D).

Outcomes

Primary Outcome Measures

Incidence of adverse events
The safety and tolerability of the supplement shall be quantified in terms of the incidence of adverse events. The frequency of adverse events and the percentage of adverse events causing subject withdrawal from the study shall be determined.

Secondary Outcome Measures

Participants with change from baseline in blood cholesterol
Significant changes in blood cholesterol will be calculated after taking each of the treatments compared to the baseline value.
Participants with change from baseline in blood homocysteine
Significant changes in blood homocysteine will be calculated after taking each of the treatments compared to the baseline value.
Participants with change from baseline in blood glycosylated haemoglobin
Significant changes in glycosylated haemoglobin will be calculated after taking each of the treatments compared to the baseline value.
Participants with change from baseline in blood Fatty acid-binding protein 2 (FABP2)
Significant changes in FABP2 will be calculated after taking each of the treatments compared to the baseline value. FABP2 will be measure using Proximity extension assay (PEA).
Change from baseline in the degree of cognitive impairment (in substudies B and C)
It will be checked whether there are significant changes in the degree of cognitive impairment after taking the treatment compared to its baseline assessment between the two treatment groups by applying The Montreal Cognitive Assessment (MOCA) test. The scores range from 0 to 30, with 26 being considered normal or greater.
Changes in Functional Ambulatory Profile (FAP) (in substudies B and C)
It will be checked whether there are significant changes in the FAP after taking the treatment compared to its baseline assessment between the two treatment groups which will be automatically measured by GAITRite® equipment before and after the Six minutes Walking Test (6MWT). FAP score is calculated by subtracting points from a maximum score of 100, being 30 the lowest possible score. In the nondisabled adult population, FAP score ranges from 95 to 100 points.
Efficacy in preventing new major cardiovascular events (in substudies B and C).
Incidence of major cardiovascular events (acute myocardial infarction, ischaemic stroke, systemic embolism or death of cardiovascular origin).
Changes in average systolic blood pressure (in substudy C)
Spacelabs' OnTrak ambulatory blood pressure monitor (ABPM) (extensively tested and validated) will measure the patient's ambulatory systolic blood pressure outside the hospital-medical setting for 24 hours after the visit and the average will be calculated.
Changes in average diastolic blood pressure (in substudy C)
Spacelabs' OnTrak ambulatory blood pressure monitor (ABPM) (extensively tested and validated) will measure the patient's ambulatory diastolic blood pressure outside the hospital-medical setting for 24 hours after the visit.
Changes in pulsatility index in middle cerebral artery (MCA) (in substudy C)
It will be checked whether there are significant changes in the pulsatility index in after taking the treatment compared to its baseline assessment between the two treatment groups. The pulsatility index (PI) is a calculated flow parameter in ultrasound, derived from the maximum, minimum, and mean transcranial Doppler frequency shifts during a defined cardiac cycle. PI = (peak systolic velocity - minimal diastolic velocity) / (mean velocity)
Efficacy in preventing new lesions related to small vessel disease from baseline (in substudy C).
Number of new lesions related to small vessel disease (white matter hyperintensities, lacunes, cerebral microbleeds or atrophy) from baseline, assessed by 3 Teslas cranial magnetic resonance imaging (MRI).
Efficacy in preventing new diffusion-weighted imaging (DWI) cerebral lesions from baseline (in substudy D)
Number of new diffusion-weighted imaging (DWI) cerebral lesions from baseline, assessed by 1.5 Teslas cranial MRI.

Full Information

First Posted
September 4, 2023
Last Updated
October 3, 2023
Sponsor
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
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1. Study Identification

Unique Protocol Identification Number
NCT06076122
Brief Title
Salicornia for Neurovascular Health Improve
Official Title
Halophyte Plants as a Dietary Supplement to Improve Neurovascular Health
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 15, 2022 (Actual)
Primary Completion Date
February 9, 2023 (Actual)
Study Completion Date
October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is evaluate the effect and safety of the administration of a food supplement based on halophyte plant extracts versus placebo in the neurovascular healthy.
Detailed Description
After being informed about the study and giving written informed consent, healthy volunteers (substudy A), patients with transient ischemic attack (TIA) or MINOR stroke (substudy B), patients with cerebral small vessel disease (substudy C) and patients who have suffered a non-disabling stroke and are going to receive carotid angioplasty and stenting (CAS) (substudy D) will be randomized in double-blind manner (participant and investigator) to take a food supplement based on halophyte plant extracts (1 g once a day) or placebo (once a day) for a treatment period of 3 months (substudy A), 11 months (substudy B), 1 year (substudy C) or 7-30 days (substudy D). Participants in substudy A will be twice as likely to be assigned to the experimental treatment as to placebo (2:1 ratio), while those in substudies B, C and D will be equally likely (1:1 ratio).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Ischemic Stroke, Neurovascular Injury, Brain Ischemia
Keywords
Polyphenol, Salicornia, Brain ischemia, Neuroprotection, Halophytes

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Multicentre, randomised, triple-blind, parallel-group, placebo-controlled pilot trial.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The BIO-DIS company in Seville prepared the extract/placebo bottles for each study arm by assigning them a unique coding for each participant that does not distinguish between extract and placebo. This coding is then the participant's study code. Treatment bottles were prepared and coded according to the ratio of dietary supplement/placebo (1:1 for Branch B, C and D and 2:1 for Branch A) and the number of participants in each branch. The list indicating which treatment (supplement/placebo) each coding corresponds to will be kept at the Hospital Universtario Virgen Macarena (HUVM) Pharmacy Service for the duration of the study. The blind will only be disclosed in the event of an adverse event (AE) that requires it and/or after completion of the analysis of the main end-points of each arm in a blinded manner.
Allocation
Randomized
Enrollment
350 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Food supplement based on Salicornia extracts
Arm Type
Experimental
Arm Description
Participants will receive food supplement based on halophyte plant (Salicornia) extracts, 1 g (two 0.5 gram capsules) orally once a day for a treatment period of 3 months (substudy A), 11 months (substudy B), 1 year (substudy C) or 7-30 days (substudy D).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive two capsules once a day of placebo physically equal to the nutritional supplement for a treatment period of 3 months (substudy A), 11 months (substudy B), 1 year (substudy C) or 7-30 days (substudy D).
Intervention Type
Dietary Supplement
Intervention Name(s)
Food supplement based on Salicornia extracts
Other Intervention Name(s)
Salicornia extracts
Intervention Description
Freshly Salicornia ramosissima plants were recollected. Its aerial part were left to dry and hydroalcoholic extracts were produced by the company Extractos Vegetales S.A. (EVESA) (Cadiz, Spain [https://evesa.com/]). The Salicornia extracts were encapsulated by BIO-DIS laboratories (Seville, Spain [https://www.bio-dis.com/]), experts in food supplements and certified for such procedures.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules physically equal to the Salicornia extracts capsules
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
The safety and tolerability of the supplement shall be quantified in terms of the incidence of adverse events. The frequency of adverse events and the percentage of adverse events causing subject withdrawal from the study shall be determined.
Time Frame
Through study completion, up to 1 year.
Secondary Outcome Measure Information:
Title
Participants with change from baseline in blood cholesterol
Description
Significant changes in blood cholesterol will be calculated after taking each of the treatments compared to the baseline value.
Time Frame
Baseline and up to 1 year.
Title
Participants with change from baseline in blood homocysteine
Description
Significant changes in blood homocysteine will be calculated after taking each of the treatments compared to the baseline value.
Time Frame
Baseline and up to 1 year.
Title
Participants with change from baseline in blood glycosylated haemoglobin
Description
Significant changes in glycosylated haemoglobin will be calculated after taking each of the treatments compared to the baseline value.
Time Frame
Baseline and up to 1 year.
Title
Participants with change from baseline in blood Fatty acid-binding protein 2 (FABP2)
Description
Significant changes in FABP2 will be calculated after taking each of the treatments compared to the baseline value. FABP2 will be measure using Proximity extension assay (PEA).
Time Frame
Baseline and up to 1 year.
Title
Change from baseline in the degree of cognitive impairment (in substudies B and C)
Description
It will be checked whether there are significant changes in the degree of cognitive impairment after taking the treatment compared to its baseline assessment between the two treatment groups by applying The Montreal Cognitive Assessment (MOCA) test. The scores range from 0 to 30, with 26 being considered normal or greater.
Time Frame
Baseline, 6 months and 1 year.
Title
Changes in Functional Ambulatory Profile (FAP) (in substudies B and C)
Description
It will be checked whether there are significant changes in the FAP after taking the treatment compared to its baseline assessment between the two treatment groups which will be automatically measured by GAITRite® equipment before and after the Six minutes Walking Test (6MWT). FAP score is calculated by subtracting points from a maximum score of 100, being 30 the lowest possible score. In the nondisabled adult population, FAP score ranges from 95 to 100 points.
Time Frame
Baseline, 6 months and 1 year.
Title
Efficacy in preventing new major cardiovascular events (in substudies B and C).
Description
Incidence of major cardiovascular events (acute myocardial infarction, ischaemic stroke, systemic embolism or death of cardiovascular origin).
Time Frame
Baseline, 6 months and 1 year.
Title
Changes in average systolic blood pressure (in substudy C)
Description
Spacelabs' OnTrak ambulatory blood pressure monitor (ABPM) (extensively tested and validated) will measure the patient's ambulatory systolic blood pressure outside the hospital-medical setting for 24 hours after the visit and the average will be calculated.
Time Frame
Baseline, 6 months and 1 year.
Title
Changes in average diastolic blood pressure (in substudy C)
Description
Spacelabs' OnTrak ambulatory blood pressure monitor (ABPM) (extensively tested and validated) will measure the patient's ambulatory diastolic blood pressure outside the hospital-medical setting for 24 hours after the visit.
Time Frame
Baseline, 6 months and 1 year.
Title
Changes in pulsatility index in middle cerebral artery (MCA) (in substudy C)
Description
It will be checked whether there are significant changes in the pulsatility index in after taking the treatment compared to its baseline assessment between the two treatment groups. The pulsatility index (PI) is a calculated flow parameter in ultrasound, derived from the maximum, minimum, and mean transcranial Doppler frequency shifts during a defined cardiac cycle. PI = (peak systolic velocity - minimal diastolic velocity) / (mean velocity)
Time Frame
Baseline, 6 months and 1 year.
Title
Efficacy in preventing new lesions related to small vessel disease from baseline (in substudy C).
Description
Number of new lesions related to small vessel disease (white matter hyperintensities, lacunes, cerebral microbleeds or atrophy) from baseline, assessed by 3 Teslas cranial magnetic resonance imaging (MRI).
Time Frame
Baseline and 1 year.
Title
Efficacy in preventing new diffusion-weighted imaging (DWI) cerebral lesions from baseline (in substudy D)
Description
Number of new diffusion-weighted imaging (DWI) cerebral lesions from baseline, assessed by 1.5 Teslas cranial MRI.
Time Frame
Final visit (from day 7 to day 30)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Substudy A: Inclusion Criteria: Patients ≥18 years old Possibility of analytical controls at the beginning/end of the study. Willingness and ability to give informed consent. Exclusion Criteria: Known neurovascular disease. Other chronic diseases for which the subject is taking medication on a regular basis. Hyperthyroidism according to the investigator's criteria. Volunteers taking vitamin or polyphenol-containing nutritional supplements in the 30 days prior to the screening visit (at the investigator's discretion). Severe illness with life expectancy of less than three months. Known allergies or intolerance to halophyte plants. Pregnant or lactating women. Presence of active neoplastic disease. Having participated in another clinical trial with medicinal products in the 30 days prior to the screening visit, or intending to do so during their participation in this study. Habitual consumption of halophyte plants. Patients who, at the investigator's discretion, are not able to comply with the study protocol. Substudy B: Inclusion criteria: Patients ≥18 years old. Patients with typical symptoms lasting less than 24 hours seen at the HUVM classified as TIA or minor stroke (if Diffusion weighted imaging (DWI) positive on magnetic resonance imaging (MRI)) during the last year. Have a neuroimaging performed at the time of the acute episode that rules out other non-vascular lesions. Willingness and ability to give informed consent. Exclusion criteria: Patients taking vitamin or polyphenol-containing nutritional supplements in the 30 days prior to the screening visit (at the investigator's discretion). Having participated in another clinical trial with medicinal products in the 30 days prior to the screening visit, or intending to do so during their participation in this study. Hyperthyroidism at the investigator's discretion. Dysphagia that prevents the intake of the study treatment. Patients dependent for basic activities of daily living (mRS >3) or with severe disease with life expectancy of less than 12 months. Known allergies or intolerance to halophyte plants. Habitual consumption of halophyte plants. Pregnant or lactating women. Presence of active neoplastic disease. Patients who, at the investigator's discretion, are unable to comply with the study protocol. Substudy C: Inclusion criteria: Patients ≥18 years of age. Lacunar syndrome with acute ischaemic lesion on neuroimaging of less than 1.5 cm maximum diameter. Willingness and ability to give informed consent. Exclusion criteria: Patients taking vitamin or polyphenol-containing nutritional supplements in the 30 days prior to the screening visit (at the investigator's discretion). Hyperthyroidism at the investigator's discretion. Claustrophobia or morbid obesity (IMT >40) precluding performance of MRI 3 Tesla. Patients dependent for basic activities of daily living (mRS >3) or with severe disease with an expected life expectancy of less than 12 months. Dysphagia that prevents the intake of the study treatment. Known allergies or intolerances to halophyte plants. Pregnant or breastfeeding women. Presence of active neoplastic disease. Having participated in another clinical trial with medicinal products in the 30 days prior to the screening visit, or intending to do so during their participation in this study. Habitual consumption of halophyte plants. Patients who, at the investigator's discretion, are not able to comply with the study protocol. Substudy D: Inclusion criteria: Patient with carotid stenosis that warrants treatment in one of the following cases: Symptomatic carotid stenosis >50% with stroke within 6 months prior to inclusion and not disabling at the time of inclusion. Asymptomatic carotid stenosis >70% provided some of the following criteria are met: I. Presence of silent stroke on neuroimaging. II. Stenosis with progression (>20%). III. Soft or ulcerated (unstable) plaque. IV. Occlusion of contralateral internal carotid artery (ICA). V. Impaired haemodynamic reserve. Receive carotid angioplasty and stenting (CAS) of said artery within a maximum of one month after inclusion and with a minimum of one week of taking the treatment from inclusion to intervention. Be able to orally take the dietary supplement/placebo from the event until just prior to the intervention. Patients ≥18 years. Willingness and ability to give informed consent. Exclusion criteria: Patients taking vitamin or polyphenol-containing nutritional supplements in the 30 days prior to the screening visit (at the investigator's discretion). Hyperthyroidism at the investigator's discretion. Claustrophobia or morbid obesity preventing the performance of MRI 1.5 Tesla. Severe disease with expected life expectancy of less than one month. Dysphagia preventing the intake of the study treatment. Known allergies or intolerance to halophyte plants. Pregnant or lactating women. Presence of active neoplastic disease. Having participated in another clinical trial with medicinal products in the 30 days prior to the screening visit, or intending to do so during their participation in this study. Habitual consumption of halophyte plants. Patients who, at the investigator's discretion, are not able to comply with the study protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joan Montaner Villalonga
Organizational Affiliation
Virgen Macarena (HUVM) and Virgen del Rocío University Hospitals (HUVR) and Institute of Biomedicine of Seville (iBIs)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana María Najar
Phone
+34 954787742
Email
anmoyano@us.es

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Analyzed data will be published as a whole
Links:
URL
http://proyectosalicornia.com/
Description
Project website

Learn more about this trial

Salicornia for Neurovascular Health Improve

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