Centella Asiatica for Cognitive Impairment

Overseen By Lucy Allison, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Oregon Health and Science University

Must be taking: Acetylcholinesterase inhibitors, Memantine

Must not be taking: Anti-epileptics, Sedatives, Anticoagulants, others

Disqualifiers: Cancer, Diabetes, CNS disease, others

Compensation: Varies

Number of Visits: 14

Duration: 6 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Centella asiatica (also known as Gotu Kola) can improve thinking skills in individuals with mild cognitive impairment or early-stage Alzheimer's. Participants will take either Centella asiatica or a placebo for six weeks to observe any noticeable changes. The trial also assesses the treatment's safety. Individuals who have experienced memory problems over the past year and have a caregiver to assist them might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but you must stop taking all botanical dietary supplements one week before and during the study. If you are on acetylcholinesterase inhibitors or memantine for Alzheimer's, you must be on a stable dose for at least 12 weeks before the trial. Some medications, like anti-epileptics, sedatives, and certain antidepressants, must be at a stable dosage for two months or are not allowed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Centella asiatica, the herb used in this trial, is generally safe. A review of several studies found no major side effects reported for Centella asiatica. Another study examined its use for people with mild memory problems or early Alzheimer's, focusing on both its safety and metabolism.

Although this trial is just starting, current evidence suggests that Centella asiatica is well-tolerated. However, participants must be closely monitored during any trial to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cognitive impairment, which often include medications like cholinesterase inhibitors or memantine, Centella asiatica is a natural plant extract. Researchers are excited about this treatment because it taps into the potential cognitive benefits of a traditional herbal remedy, which is thought to enhance memory and cognitive function without the side effects commonly associated with pharmaceutical drugs. The treatment is administered as a simple drink, making it an easy and non-invasive option for patients. Additionally, it introduces a new mechanism of action by potentially promoting nerve growth and repair, which is different from the current drugs that mainly focus on neurotransmitter regulation.

What evidence suggests that Centella asiatica might be an effective treatment for cognitive impairment?

Research has shown that Centella asiatica, also known as Gotu kola, might help improve brain function. One study found that daily Gotu kola extract improved thinking problems after a stroke. Another study showed that taking Centella asiatica for 20 weeks enhanced memory and speaking skills in older women with dementia. Additionally, consuming Centella asiatica increased alertness and feelings of happiness shortly after intake. This trial will compare the effects of a Centella asiatica water extract product with a placebo to evaluate its potential benefits for cognitive impairment. These findings suggest that Centella asiatica could improve brain abilities in various groups. ^{4 6 7 8 9}

Who Is on the Research Team?

Amala Soumyanath, PhD

Principal Investigator

Oregon Health and Science University

Joseph Quinn, MD

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

This trial is for people aged 65-85 with mild cognitive impairment or early Alzheimer's, who can speak English and have good vision and hearing. They must not be allergic to Centella asiatica, have a BMI of 17-35, no severe depression or suicidal thoughts, stable health, and agree to stop taking botanical supplements. Participants need an informant to confirm memory decline and a caregiver for visits.

Inclusion Criteria

Total score of <2 on the suicidal ideation subscale (measures 3, 7, 11, 12 and 14) of the Geriatric Depression Scale

Willingness to discontinue all botanical dietary supplements for one week prior to and during the study

Participants who report a history of participative memory decline with gradual onset and slow progression over the last one year before screening MUST be corroborated by an informant

Exclusion Criteria

I have conditions like diabetes, kidney or liver failure, hepatitis, blood disorders, low blood pressure when standing, or heart disease.

I am a man not planning to father a child within three months after the study ends.

Severe aversion to venipuncture

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Centella asiatica water extract or placebo daily for 6 weeks

6 weeks

Baseline and after 6 weeks of daily intervention

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Visits at 8 weeks and 10 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Centella asiatica product
• Placebo

Trial Overview The study tests if a water extract of Centella asiatica taken orally for six weeks shows biological signs of improving cognition compared to placebo. It also checks the safety and how well participants tolerate the treatment. The trial includes multiple MRI scans.

How Is the Trial Designed?

Group I: Centella asiatica water extract product (CAP) 4g Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Published Research Related to This Trial

In a study of 48 patients with poststroke cognitive impairment, both doses of gotu kola (1000 mg and 750 mg per day) were found to effectively improve cognitive function, as measured by the Montreal Cognitive Assessment (MoCA-Ina) after 6 weeks.

Gotu kola was particularly effective in enhancing memory compared to folic acid, suggesting it could be a beneficial treatment option for improving cognitive function in patients with vascular cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Gotu Kola Extract 750 mg and 1000 mg Compared with Folic Acid 3 mg in Improving Vascular Cognitive Impairment after Stroke. Farhana, KM., Malueka, RG., Wibowo, S., et al.[2020]

Centella asiatica water extract (CAW) significantly improved cognitive performance in older mice, as demonstrated by better results in the Morris Water Maze test, while also showing modest benefits in younger mice.

CAW treatment led to increased expression of genes related to mitochondrial function and antioxidant responses in both young and old mice, suggesting that these mechanisms may contribute to the observed cognitive enhancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Centella asiatica modulates antioxidant and mitochondrial pathways and improves cognitive function in mice. Gray, NE., Harris, CJ., Quinn, JF., et al.[2021]

In a study involving 64 male rats, treatment with 20 mg/kg of Centella asiatica extract improved cognitive deficits and reduced neuronal damage in the hippocampus caused by chronic cerebral hypoperfusion, both when administered shortly after the insult and even after a year.

The extract was effective in enhancing learning flexibility and memory, indicating its potential as a therapeutic option for cognitive impairments related to reduced blood flow to the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Centella asiatica on pathophysiology of mild chronic cerebral hypoperfusion in rats. Thong-Asa, W., Tilokskulchai, K., Chompoopong, S., et al.[2022]

In a study involving adult rats, treatment with higher doses (6 ml/kg) of Centella asiatica fresh leaf extract for 6 weeks significantly improved spatial learning and memory retention, as evidenced by better performance in T-Maze tests.

The results showed that these rats had increased alternations and less time spent in the small compartment during memory tests, indicating enhanced cognitive abilities compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with Centalla asiatica (Linn) fresh leaf extract enhances learning ability and memory retention power in rats. Rao, MK., Rao, MS., Rao, GS.[2011]

Long-term treatment with a water extract of Centella asiatica (CAW) for three months improved cognitive functions and reduced amyloid-β plaque levels in a mouse model of Alzheimer's disease, indicating its potential as a therapeutic agent.

The cognitive benefits of CAW are likely linked to the activation of the NRF2 antioxidant pathway, as blocking NRF2 with an inhibitor diminished the positive effects on synaptic plasticity, suggesting that targeting NRF2 could be a promising strategy for enhancing cognitive function in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged Treatment with Centella asiatica Improves Memory, Reduces Amyloid-β Pathology, and Activates NRF2-Regulated Antioxidant Response Pathway in 5xFAD Mice. Zweig, JA., Brandes, MS., Brumbach, BH., et al.[2021]

A water extract of Centella asiatica (GKW) showed promise in reducing behavioral issues related to β-amyloid in a mouse model of Alzheimer's disease, suggesting potential therapeutic benefits for cognitive function.

GKW protected neuroblastoma cells from β-amyloid toxicity and prevented the formation of harmful β-amyloid aggregates, indicating a unique mechanism of action that differs from current Alzheimer's treatments, which typically focus on anticholinesterase activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action. Soumyanath, A., Zhong, YP., Henson, E., et al.[2021]

Centella asiatica, commonly known as Gotu Kola, has demonstrated significant neuroprotective effects through various mechanisms, including enzyme inhibition and prevention of amyloid plaque formation associated with Alzheimer's disease.

The plant also shows potential in reducing dopamine neurotoxicity in Parkinson's disease and decreasing oxidative stress, suggesting it could be a valuable phytopharmaceutical for brain health based on traditional medicinal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Centella asiatica (L.) Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential. Orhan, IE.[2023]

Centella asiatica, a botanical product known for its cognitive enhancement properties in traditional medicine, shows promise as a treatment for cognitive decline and Alzheimer's disease based on preclinical studies that highlight its effects on antioxidant response and mitochondrial activity.

The development of a clinical-grade Centella asiatica product involves addressing challenges such as optimal dosing, product characterization, and regulatory approvals, emphasizing the complexity of translating botanical research into effective clinical therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges. Wright, KM., McFerrin, J., Alcázar Magaña, A., et al.[2023]

A systematic review of 11 randomized controlled trials found that Centella asiatica does not significantly improve cognitive function compared to placebo, indicating limited evidence for its use in enhancing memory or cognitive abilities.

However, C. asiatica may improve mood by increasing alertness and reducing anger shortly after treatment, with no reported adverse effects, suggesting it could have some beneficial effects on emotional well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis. Puttarak, P., Dilokthornsakul, P., Saokaew, S., et al.[2021]

In a study involving 20 male rats subjected to chronic electrical stress, treatment with 600 mg/kg of Centella asiatica (Gotu kola) significantly improved memory performance, as evidenced by reduced escape latency in the Morris water maze test.

The improvement in memory was linked to increased levels of brain-derived neurotrophic factor (BDNF) and activation of the TrkB and ERK1/2 signaling pathways in the hippocampus, suggesting a mechanism for the neuroprotective effects of Gotu kola.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Centella asiatica (Gotu kola) ethanol extract up-regulates hippocampal brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling in chronic electrical stress model in rats. Sari, DCR., Arfian, N., Tranggono, U., et al.[2022]

In a randomized, placebo-controlled study with 28 healthy elderly participants, Centella asiatica at a high dose (750 mg) improved working memory and enhanced brain activity as measured by the N100 component of event-related potentials over 2 months.

Participants also reported improvements in mood after treatment with Centella asiatica, suggesting its potential benefits for cognitive function and mood in aging individuals, although the exact mechanisms of action need further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. Wattanathorn, J., Mator, L., Muchimapura, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4908235/

Effectiveness of Gotu Kola Extract 750 mg and 1000 ... This study concluded that a gotu kola extract therapy of 1000 mg/day and 750 mg/day is effective in improving cognitive impairment after stroke infarction.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9650315/

Does Gotu kola supplementation improve cognitive function ... Although Gotu kola supplementation had no additional effects on increased cognitive function, the results revealed a significant relationship between the change ...

3. nature.com nature.com/articles/s41598-017-09823-9

Effects of Centella asiatica (L.) Urb. on cognitive function ... Effectiveness of Gotu Kola Extract 750 mg and 1000 mg Compared with Folic Acid 3 mg in Improving Vascular Cognitive Impairment after Stroke.

4. iopscience.iop.org iopscience.iop.org/article/10.1088/1755-1315/755/1/012064

Twenty weeks of Centella asiatica improved cognitive ... In conclusion, administration of Centella asiatica for 20 weeks is effective in increasing semantic fluency and visual memory in women elderly with dementia.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1756464620305612

Consumption of fresh Centella asiatica improves short term ... Consumption of a smoothie containing Centella asiatica improves alertness and contentedness after one hour. No effect was observed on cognitive performance.

6. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Centella-asiatica-Cognitive-Vitality-For-Researchers.pdf

Centella asiatica (Gotu kola) In a rat model of cognitive decline (streptozotocin injection), Centella asiatica treatment (100-300 mg/kg) showed a dose-dependent improvement in cognitive ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3116297/

Pharmacological Review on Centella asiatica: A Potential ... The mean MMSE scoring showed significant improvement after administration of CA for 6 months in elderly with mild cognitive impairment (MCI) at dosage of 500 mg ...

8. withpower.com withpower.com/trial/phase-1-mild-cognitive-impairment-mci-10-2022-c4600

Centella Asiatica for Cognitive Impairment The systematic review and meta-analysis of Centella asiatica for cognitive function found no significant adverse effects reported in the studies reviewed.

9. ohsu.edu ohsu.edu/school-of-medicine/neurology/safety-and-target-engagement-centella-asiatica-cognitive-impairment

Safety and Target Engagement of Centella asiatica in ... A Phase I clinical study to explore the safety and biological activity of Centella asiatica in individuals with MCI or mild Alzheimer's.