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| Name | Class |
|---|---|
| Alzheimer's Association | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Centella asiatica water extract product (CAP) 4g | Experimental | A 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. |
|
| Placebo | Placebo Comparator | A 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Centella asiatica product | Drug | A sachet of powdered product containing 4 g of a dried hot water extract of Centella asiatica as the active ingredient, combined with inactive ingredients (excipients) for color and taste dissolved in 10 oz of warm or room temperature water and consumed orally. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in brain N-acetylaspartate (NAA) to creatine (Cr) metabolite ratio (NAA/Cr) after 6 weeks on intervention. | 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. | Baseline and 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in urinary 8-hydroxy-2-deoxyguanosine (8 OHdG)/creatinine ratio after 6 weeks on intervention. | 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. | Baseline and 6 weeks |
| Change from baseline in plasma 8-hydroxy-2-deoxyguanosine (8-OhdG) after 6 weeks on intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in cortical and hippocampal levels of Adenosine triphosphate (ATP)/total phosphate after 6 weeks on intervention. | Cortical and hippocampal levels of ATP as a proportion of total phosphate as detected through 31P- Magnetic Resonance Spectroscopic Imaging. | Baseline and 6 weeks |
| Change from baseline in cortical and hippocampal levels of phosphocreatine (PCr)/total phosphate after 6 weeks on intervention. |
Inclusion criteria:
Exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Amala Soumyanath, PhD | Contact | 503-494-6878 | soumyana@ohsu.edu | |
| Lucy Allison, MS | Contact | 503-418-8197 | allisolu@ohsu.edu |
| Name | Affiliation | Role |
|---|---|---|
| Amala Soumyanath, Ph.D | Oregon Health and Science University | Principal Investigator |
| Joseph Quinn, MD | Oregon Health and Science University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oregon Health & Science University | Recruiting | Portland | Oregon | 97239 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35096945 | Background | Wright KM, McFerrin J, Alcazar Magana A, Roberts J, Caruso M, Kretzschmar D, Stevens JF, Maier CS, Quinn JF, Soumyanath A. Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges. Front Nutr. 2022 Jan 14;8:799137. doi: 10.3389/fnut.2021.799137. eCollection 2021. | |
| 35204098 |
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There is no plan to release individual participant data.
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003704 | Dementia |
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48 participants will be randomized to receive either Centella asiatica water extract product (CAP) or placebo treatment. Participants will be stratified by sex so that CAP and placebo arms have equal numbers of each sex.
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Drug product and placebo will be prepared at Oregon's Wild Harvest using a formula that matches taste, smell, and appearance. The Research Pharmacy at Oregon Health and Science University will maintain information on product allocation (drug or placebo) to individual participants.
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| Placebo | Drug | A sachet of powdered inactive ingredients (excipients) for color and taste identical in volume to those found in the active arm (CAP) dissolved in 10 oz of warm or room temperature water and consumed orally. |
|
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. |
| Baseline and 6 weeks |
| Adverse events (AE) arising during, and up to 4 weeks after, 6 weeks on intervention. | 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. | Baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks and 10 weeks |
| Oral temperature measured at study visits. | 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. | Baseline and 6 weeks |
| Pulse rate measured at study visits. | 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. | Baseline and 6 weeks |
| Change from baseline in seated blood pressure after 6 weeks on intervention. | 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. | Baseline and 6 weeks |
| Change from baseline in body mass index after 6 weeks on intervention. | 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. | Baseline and 6 weeks |
| Change from baseline in electrocardiography signals after 6 weeks on intervention. | 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. | Baseline and 6 weeks |
| Change from baseline liver function after 6 weeks on intervention. | 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. | Baseline and 6 weeks |
| Change from baseline in kidney function after 6 weeks on intervention. | 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. | Baseline and 6 weeks |
Cortical and hippocampal levels of phosphocreatine (PCr) as a proportion of total phosphate as detected through 31P- Magnetic Resonance Spectroscopic Imaging. |
| Baseline and six weeks |
| Change from baseline in cortical and hippocampal levels of inorganic phosphate (Pi)/total phosphate after 6 weeks on intervention. | Cortical and hippocampal levels of inorganic phosphate (Pi) as a proportion of total phosphate as detected through 31P- Magnetic Resonance Spectroscopic Imaging. | Baseline and 6 weeks |
| Change from baseline in cortical and hippocampal phosphocreatine/inorganic phosphate ratio (PCr/Pi) after 6 weeks on intervention. | Ratio of Cortical and hippocampal levels of phosphocreatine and inorganic phosphate as detected through 31P- Magnetic Resonance Spectroscopic Imaging. | Baseline and 6 weeks |
| Wright KM, Bollen M, David J, Speers AB, Brandes MS, Gray NE, Alcazar Magana A, McClure C, Stevens JF, Maier CS, Quinn JF, Soumyanath A. Pharmacokinetics and Pharmacodynamics of Key Components of a Standardized Centella asiatica Product in Cognitively Impaired Older Adults: A Phase 1, Double-Blind, Randomized Clinical Trial. Antioxidants (Basel). 2022 Jan 23;11(2):215. doi: 10.3390/antiox11020215. |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |