Emtricitabine for Alzheimer's Disease

(LINE-AD Trial)

Recruiting at 1 trial location

Overseen By Meghan Riddle, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Butler Hospital

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: Immunosuppressives, Antipsychotics

Disqualifiers: Parkinson's, Schizophrenia, Bipolar, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized, double-blind clinical trial of a daily oral dose of 200 mg emtricitabine vs. placebo in 35 participants with biomarker-confirmed MCI or mild to moderate dementia due to Alzheimer's disease. Study duration for each subject participating in the placebo-controlled research study will be approximately 12 months (up to a 3 months Screening Period, Baseline visit (1 month), 6 months of placebo or emtricitabine dosing, and 1 month follow-up). Participants will have up to 2 months to complete all procedures for the month 6 study visit.

Do I need to stop my current medications to join the trial?

The trial allows participants to continue taking cholinesterase inhibitors and memantine if they have been on a stable dose for at least 60 days before starting the trial. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

How is the drug Emtricitabine unique in treating Alzheimer's disease?

Emtricitabine is unique in Alzheimer's treatment because it is originally an antiretroviral drug used for HIV, suggesting a novel approach by potentially targeting similar pathways involved in brain injury, unlike traditional Alzheimer's drugs that focus on amyloid plaques. ^{1 2 3 4 5}

Research Team

Meghan Riddle, MD

Principal Investigator

Butler Hospital

John Sedivy, PhD

Principal Investigator

Brown University

Eligibility Criteria

This trial is for people aged 50-85 with mild cognitive impairment or mild to moderate dementia due to Alzheimer's, confirmed by specific biomarkers. Participants need a reliable study partner and must have been on stable doses of certain Alzheimer's medications for at least 60 days. Exclusions include other significant neurological conditions, recent drug abuse, major organ toxicity risk from other drugs, severe heart/liver/kidney disease, pregnancy/breastfeeding, and certain psychiatric risks.

Inclusion Criteria

Your cerebrospinal fluid (CSF) test must show a pTau/Aβ42 ratio of more than 0.024.

Participants must have an appropriate study partner who agrees to participate in the study and who is intellectually, visually, and auditory capable, and fluent in, and able to read, the language in which study assessments are administered. Additionally, the study partner must be capable of and willing to: Accompany the participant to visits that requires the input of the study partner

Intellectually, visually and auditory capable, fluent in, and able to read, the language in which study assessments are administered (e.g. completion of at least six years of regular schooling or sustained employment or equivalent local level of knowledge)

Exclusion Criteria

I do not have any conditions affecting my thinking or memory.

Your brain MRI shows something that could cause future memory problems, could be risky for you, or could make it hard to monitor your safety during the study.

In the past six months, you have had thoughts of suicide or have engaged in suicidal behavior in the past two years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 3 months

1 visit (in-person)

Baseline

Baseline assessments are conducted before treatment begins

1 month

1 visit (in-person)

Treatment

Participants receive a daily oral dose of 200 mg emtricitabine or placebo

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 visit (in-person)

Treatment Details

Interventions

• Emtricitabine

Trial Overview The trial tests the effectiveness of Emtricitabine (200 mg daily) against a placebo in improving cognitive function over approximately one year. It involves participants who meet specific criteria related to Alzheimer's Disease and includes regular monitoring through visits and follow-ups.

Participant Groups

Group I: Group 1 Active Control 1 Intervention

25 MCI and mild to moderate AD subjects

Group II: Group 2 Placebo Group 1 Intervention

10 MCI and mild to moderate AD subjects

Emtricitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Emtriva for:

• HIV-1 infections

Approved in United States as Emtriva for:

• HIV-1 infections
• Pre-exposure prophylaxis of HIV-1

Approved in Canada as Emtriva for:

• HIV-1 infections

Approved in Japan as Emtriva for:

• HIV-1 infections

Who Is Running the Clinical Trial?

Butler Hospital

Lead Sponsor

Trials

133

Recruited

16,700+

Cedars Sinai Medical Center, Los Angeles, USA

Collaborator

Trials

1

Recruited

500+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Brown University

Collaborator

Trials

480

Recruited

724,000+

The Miriam Hospital

Collaborator

Trials

252

Recruited

39,200+

Findings from Research

Idalopirdine, a selective 5-HT6 receptor antagonist, showed no significant overall efficacy in improving cognitive function in Alzheimer's disease patients compared to placebo, based on a meta-analysis of 4 randomized controlled trials involving 2,803 participants.

While idalopirdine may have some effectiveness at higher doses and in patients with moderate Alzheimer's, it is associated with a higher risk of adverse events, including elevated liver enzymes and vomiting, raising concerns about its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of idalopirdine for Alzheimer's disease: a systematic review and meta-analysis. Matsunaga, S., Fujishiro, H., Takechi, H.[2020]

AIDS dementia remains a significant complication of HIV-1 infection, with an estimated incidence of 3-8 cases per 100,000 people, highlighting the need for effective treatments despite the availability of antiretroviral therapy.

Current research is limited by a lack of large, well-controlled clinical trials for neuroprotective agents, indicating a critical gap in understanding and addressing the brain injury associated with HIV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological frontiers in the treatment of AIDS dementia. McGuire, D., Marder, K.[2017]

Aducanumab, the first FDA-approved therapy for Alzheimer's disease, has been shown to reduce clinical decline in patients with mild cognitive impairment and mild dementia, based on data from the phase 3 EMERGE trial.

Long-term modeling predicts that aducanumab treatment can lead to significant benefits, including an increase of 0.65 quality-adjusted life-years (QALYs) per patient and a delay in the progression to more severe stages of Alzheimer's, providing both clinical and socioeconomic advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease. Herring, WL., Gould, IG., Fillit, H., et al.[2022]

In a study involving 125 patients with mild to moderate Alzheimer's disease, MLC901 (NeuroAiD II) was found to be safe as an add-on therapy, with no significant increase in serious adverse events compared to placebo over 12 months.

While early treatment with MLC901 did not show significant cognitive improvements compared to placebo, the study suggests potential for slowing disease progression, warranting further research with larger trials and biomarker assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alzheimer's Disease THErapy With NEuroaid (ATHENE): A Randomized Double-Blind Delayed-Start Trial. Chen, CLH., Lu, Q., Moorakonda, RB., et al.[2022]

In a Phase III trial involving 105 AIDS dementia complex (ADC) patients, adding abacavir (ABC) to stable background antiretroviral therapy (SBG) did not show significant efficacy in improving neuropsychological function after 12 weeks, with similar outcomes in both ABC and placebo groups.

The study revealed that two-thirds of participants had baseline resistance to ABC, and many patients experienced prolonged benefits from existing therapy, which may have contributed to the lack of observed efficacy and highlights the importance of considering drug resistance and patient stability in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors in AIDS dementia complex trial design: results and lessons from the abacavir trial. Brew, BJ., Halman, M., Catalan, J., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of idalopirdine for Alzheimer's disease: a systematic review and meta-analysis. [2020]

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

Pharmacological frontiers in the treatment of AIDS dementia. [2017]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease. [2022]

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

Alzheimer's Disease THErapy With NEuroaid (ATHENE): A Randomized Double-Blind Delayed-Start Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Factors in AIDS dementia complex trial design: results and lessons from the abacavir trial. [2020]