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Safety and Target Engagement of Centella Asiatica in Cognitive Impairment

Phase 1
Recruiting
Conditions
Mild Cognitive Impairment
Alzheimer's Disease
Interventions
Drug: Centella asiatica product
Drug: Placebo
Registration Number
NCT05591027
Lead Sponsor
Oregon Health and Science University
Brief Summary

This clinical trial is focused on determining whether biological signatures of target engagement by a Centella asiatica water extract product administered orally for 6 weeks can be measured in comparison to placebo. This study will also assess the safety and tolerability of the Centella asiatica water extract product.

Detailed Description

This Phase I study is a randomized, double-blind, placebo-controlled, clinical trial of 48 participants to evaluate safety, tolerability, and biological signatures of target engagement of brain neuronal viability, oxidative stress, and brain mitochondrial activity of a Centella asiatica water extract product (CAP) in older adults aged 60-85 years with mild cognitive impairment or mild Alzheimer's disease (AD). The intervention is taken orally daily for six weeks and pre and post assessments will be collected.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
48
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Centella asiatica water extract product (CAP) 4gCentella asiatica productA sachet of containing 4g dried hot water extract (CAW) of Centella asiatica combined with inactive ingredients (excipients) will be dissolved in water and orally consumed daily as a drink for six weeks. Assessments will be collected at baseline and after six weeks of daily intervention.
PlaceboPlaceboA sachet of inactive ingredients (excipients) identical in composition to those found in the active arm will be be dissolved in water and orally consumed daily for six weeks. Assessments will be collected at baseline and after six weeks of daily intervention.
Primary Outcome Measures
NameTimeMethod
Change from baseline in brain N-acetylaspartate (NAA) to creatine (Cr) metabolite ratio (NAA/Cr) after 6 weeks on intervention.Baseline and 6 weeks

N-acetylaspartate (NAA)/creatine (Cr) metabolite ratio (NAA/Cr) in the brain determined through 1H-Magnetic Resonance Spectroscopic Imaging of a single brain slice as an indicator of neuronal viability and mitochondrial activity.

Secondary Outcome Measures
NameTimeMethod
Change from baseline in urinary 8-hydroxy-2-deoxyguanosine (8 OHdG)/creatinine ratio after 6 weeks on intervention.Baseline and 6 weeks

Ratio of 8-hydroxy-deoxyguanosine (8 OHdG) to creatinine in urine, as a measure of oxidative stress as determined by means of enzyme linked immunosorbent assay.

Change from baseline in plasma 8-hydroxy-2-deoxyguanosine (8-OhdG) after 6 weeks on intervention.Baseline and 6 weeks

A peripheral venous sample will be collected. Levels of plasma 8-hydroxy-deoxyguanosine will be determined by means of the 8-hydroxy-2-deoxyguanosine enzyme linked immunosorbent assay as a measure of oxidative stress.

Adverse events (AE) arising during, and up to 4 weeks after, 6 weeks on intervention.Baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks and 10 weeks

A standard multi-system questionnaire will record the type and severity (range 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) of any adverse events. The Investigators will evaluate any changes in symptoms from baseline, and consider alternative clinical explanations, to determine if the changes are adverse events attributable to the study intervention. The investigators will determine the proportion of participants who report each type of adverse event following administration of CAP compared to placebo.

Oral temperature measured at study visits.Baseline and 6 weeks

Oral temperature will be measured in degrees Celsius by means of a thermometer. Temperatures falling outside the normal range (33.2-38.2 degrees Celsius) will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if they are attributable to the study intervention. The investigators will determine the proportion of all participants who develop changes in temperature following administration of CAP compared to placebo.

Pulse rate measured at study visits.Baseline and 6 weeks

Pulse rate will be measured peripherally over one minute. Pulse rates falling outside the normal range (60-80 beats per minute) will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if they are attributable to the study intervention. The investigators will determine the proportion of all participants who develop changes in pulse rate following administration of CAP compared to placebo.

Change from baseline in seated blood pressure after 6 weeks on intervention.Baseline and 6 weeks

Seated blood pressure will be measured in millimeters mercury. Blood pressure readings falling outside the normal range (90-130/60-80 millimeters Mercury) will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if they are attributable to the study intervention. The investigators will determine the proportion of all participants who develop changes in blood pressure following administration of CAP compared to placebo.

Change from baseline in body mass index after 6 weeks on intervention.Baseline and 6 weeks

Height in centimeters and weight in kilograms will be measured and aggregated to measure body mass index in kilograms per meter squared (kg/m2). Changes in body mass index greater than two kilograms per meter squared from baseline levels, along with consideration of alternative clinical explanations, will be used to determine attribution to the study intervention. The investigators will determine the proportion of all participants who develop changes in body mass index of greater than two units (kilograms per meter squared) following administration of CAP compared to placebo.

Change from baseline in electrocardiography signals after 6 weeks on intervention.Baseline and 6 weeks

Resting electrocardiography will be measured for up to five minutes using a five lead mobile electrocardiogram. Changes in P wave shape or length, QRS complex shape or length, and QT interval from baseline will be measured, and alternative clinical explanations considered, in order to determine if any changes are attributable to the study intervention. The investigators will determine the proportion of all participants who develop changes in electrocardiography from baseline following CAP administration compared to placebo.

Change from baseline liver function after 6 weeks on intervention.Baseline and 6 weeks

A comprehensive metabolic panel will measure alanine aminotransferase and aspartate aminotransferase in units per liter as markers of liver function. Enzyme levels falling outside the normal range (0-35 Units per liter for alanine aminotransferase and 17-59 Units per liter for aspartate aminotransferase) will be compared to baseline levels, and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. The investigators will aggregate the measures by using an elevation in either enzyme function as a reflection of overall liver function. The investigators will determine the proportion of all participants who develop abnormal laboratory values following administration of CAP compared to placebo.

Change from baseline in kidney function after 6 weeks on intervention.Baseline and 6 weeks

A comprehensive metabolic panel will measure creatinine and blood urea nitrogen levels in milligrams per deciliter as markers of kidney function. Each parameter falling outside the normal range ( 0.5 to 1.2 milligrams per deciliter for creatinine and 7 to 20 milligrams per deciliter for blood urea nitrogen), will be compared to baseline values and alternative clinical explanations considered, in order to determine if elevations are attributable to the study intervention. The investigators will aggregate the measures by using an elevation in either blood urea nitrogen or creatinine as a reflection of overall kidney function. The investigators will determine the proportion of all participants who develop abnormal laboratory values following administration of CAP compared to placebo.

Trial Locations

Locations (1)

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

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