AGB101 for Dementia

(AGB101-CN Trial)

Overseen By Caroline L Wagandt, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Anticonvulsants, Anticoagulants

Disqualifiers: Neurological disease, Major depression, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized, crossover, placebo controlled clinical study will assess the efficacy and safety of a slow release form of levetiracetam (AGB101) in the treatment of cognitively normal adults by measuring change in several imaging measures over the course of a two week treatment period.

Will I have to stop taking my current medications?

The trial requires that you stop taking anticonvulsant or anticoagulant medications at least 1 month before starting. If you're on antidepressants, the dose must be stable for 1 month before and during the study.

What data supports the effectiveness of the drug AGB101 for dementia?

Research on similar treatments like galantamine and EGb 761 shows they can help maintain daily living activities and improve cognitive performance in Alzheimer's patients, suggesting potential benefits for AGB101 in dementia. ^{1 2 3 4 5}

Is AGB101 (galantamine) safe for humans?

Galantamine, which may be related to AGB101, has been shown to be generally safe in humans, with side effects that are usually mild to moderate and mostly related to the stomach. It has been tested in people with Alzheimer's and other types of dementia. ^{6 7 8 9 10}

How does the drug AGB101 differ from other treatments for dementia?

AGB101 is unique because it may target lysosomal dysfunction, a process linked to genetic risk factors like GBA1 mutations, which are associated with dementia with Lewy bodies. This approach could offer a novel mechanism of action compared to existing treatments that primarily focus on symptoms rather than underlying genetic and molecular causes. ^{11 12 13 14 15}

Research Team

Arnold Bakker, Ph.D.

Principal Investigator

Johns Hopkins University

Marilyn Albert, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for cognitively normal adults aged 50-80 with no memory complaints, good general health, and a reliable study partner. They must be able to undergo PET and MRI scans, have stable antidepressant use if applicable, and agree to effective contraception if of childbearing age. Exclusions include recent participation in other clinical studies, significant neurological diseases or conditions that might interfere with the study, major depression within the last 3 years or psychotic disorders history.

Inclusion Criteria

Subjects must be willing and able to undergo a Tau positron emission tomography (PET) scan with 18F MK-6240 tracer

I am between 50 and 80 years old and in good health.

I am willing and able to follow the study requirements.

Exclusion Criteria

Subjects must not have any other reason, which in the opinion of the investigator, would confound proper interpretation of the study

I haven't taken any seizure or blood thinner medications in the last month.

Subjects must not participate in a therapeutic clinical study for any medical or psychiatric indications within 1 month of the screening visit or at any time during the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AGB101 or placebo once daily for 2 weeks

2 weeks

1 visit (in-person) at the end of each treatment period

Washout

Participants undergo a washout period between treatment phases

4 weeks

Crossover Treatment

Participants receive the alternate treatment (AGB101 or placebo) once daily for 2 weeks

2 weeks

1 visit (in-person) at the end of each treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AGB101

Trial Overview AGB101 (a slow-release form of levetiracetam) is being tested for its ability to reduce hippocampal overactivity in older adults without dementia. The trial uses a randomized crossover design where participants receive both AGB101 and placebo at different times during the two-week treatment period while undergoing imaging measures.

Participant Groups

Group I: placebo first, then AGB101 Experimental Treatment 2 Interventions

Placebo capsule once daily for 2 weeks, washout (4 weeks), then AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 2 weeks.

Group II: AGB101 first, then placebo Experimental Treatment 2 Interventions

AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 2 weeks, washout (4 weeks), then placebo capsule once daily for 2 weeks.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

AgeneBio

Industry Sponsor

Trials

3

Recruited

250+

References

1. United States pubmed.ncbi.nlm.nih.gov

Galantamine maintains ability to perform activities of daily living in patients with Alzheimer's disease. [2016]

2. Germany pubmed.ncbi.nlm.nih.gov

Response patterns of EGb 761 in Alzheimer's disease: influence of neuropsychological profiles. [2016]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Effects of GV1001 on Language Dysfunction in Patients With Moderate-to-Severe Alzheimer's Disease: Post Hoc Analysis of Severe Impairment Battery Subscales. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Influence of the severity of cognitive impairment on the effect of the Gnkgo biloba extract EGb 761 in Alzheimer's disease. [2018]

6. Spain pubmed.ncbi.nlm.nih.gov

[Observational study on safety, tolerability and effectiveness of galantamine in patients with mild to moderately severe Alzheimer's disease]. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

The clinical efficacy and safety of galantamine in the treatment of Alzheimer's disease. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Long-term outcomes of galantamine treatment in patients with Alzheimer disease. [2019]

10. India pubmed.ncbi.nlm.nih.gov

Galantamine: a review of its use in Alzheimer's disease and vascular dementia. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Dementia with Lewy bodies - from scientific knowledge to clinical insights. [2022]

13. France pubmed.ncbi.nlm.nih.gov

[Heterogeneity of Alzheimer's disease]. [2006]

14. United States pubmed.ncbi.nlm.nih.gov

Exploring the link between GBA1 mutations and Dementia with Lewy bodies, A mini-review. [2022]

15. England pubmed.ncbi.nlm.nih.gov

Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies. [2023]