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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether emtricitabine can help individuals with early-stage Alzheimer's disease or mild memory issues related to Alzheimer's. Participants will take either emtricitabine or a placebo (a pill with no active drug) for six months to assess improvements in memory and thinking. It suits individuals aged 50-85 diagnosed with mild cognitive issues due to Alzheimer's who have a study partner to assist with trial activities. The aim is to find a new way to manage symptoms and potentially slow the disease's progression. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

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.

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

Research has shown that emtricitabine is generally safe for people. It has been used safely in treating HIV, and a small study also tested it for Alzheimer's. This study found that emtricitabine was safe and did not cause any major side effects.

The current study is in an early stage, focusing primarily on the treatment's safety. If earlier research had uncovered serious issues, this study likely would not proceed. While more testing is necessary, early results suggest that emtricitabine is safe for individuals with mild cognitive impairment or Alzheimer's. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Emtricitabine is unique because, unlike most current Alzheimer's treatments that focus on managing symptoms or targeting amyloid plaques, it is primarily known as an antiretroviral medication used in treating HIV. Researchers are excited because emtricitabine may offer a novel approach by potentially impacting the underlying mechanisms of Alzheimer's disease, such as neuroinflammation or viral infections that have been hypothesized to play a role in its progression. This fresh perspective could pave the way for new therapeutic strategies that are different from traditional therapies like cholinesterase inhibitors or NMDA receptor antagonists.

What evidence suggests that emtricitabine might be an effective treatment for Alzheimer's disease?

Research suggests that emtricitabine, which participants in this trial may receive, might help treat Alzheimer's disease. Studies have shown that people who took similar drugs, called nucleoside reverse transcriptase inhibitors, had a lower chance of developing Alzheimer's. This indicates that emtricitabine could potentially protect against the disease. While researchers are still gathering direct evidence on emtricitabine's effectiveness for Alzheimer's, it has shown promise in treating other conditions. The treatment might help reduce the harmful effects in the brain linked to Alzheimer's. ^{1 6 7 8 9}

Who Is on the Research Team?

Meghan Riddle, MD

Principal Investigator

Butler Hospital

John Sedivy, PhD

Principal Investigator

Brown University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. butler.org butler.org/studies/line-ad

Repurposing Nucleoside Reverse Transcriptase Inhibitors ... The purpose of this study is to look at the safety and tolerability of Emtricitabine (FTC, Emtriva©, Gilead) in treating participants with MCI or mild to ...

2. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/STUDY00003008

Repurposing Nucleoside Reverse Transcriptase Inhibitors for ... The purpose of this study is to determine whether a medication called emtricitabine is safe and tolerable in people with mild to moderate Alzheimer's.

3. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70180

Association of nucleoside reverse transcriptase inhibitor use ... We report that in humans, NRTI exposure was associated with a significantly lower incidence of AD in two of the largest health insurance databases in the ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04500847?intr=EMTRIVA&aggFilters=studyType:int&viewType=Table&rank=1

Repurposing Nucleoside Reverse Transcriptase Inhibitors ... 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11040692/

Alzheimer's disease drug development pipeline: 2024 - PMC On the Index Date of January 1, 2024, there were 164 clinical trials for AD (prevention, MCI, AD dementia) assessing 127 drugs. This included 48 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10925371/

A pilot study to investigate the safety and feasibility of ... A pilot study to investigate the safety and feasibility of antiretroviral therapy for Alzheimer's disease (ART-AD)

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07210528

Safety Of Nrtis for Alzheimer's Therapeutic Advancement in ... A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Emtricitabine and Descovy in Patients With Mild ...

8. nature.com nature.com/articles/s44400-024-00001-z

A Phase IIa clinical trial to evaluate the effects of anti- ... LINE-AD, a phase 1 study in which emtricitabine is being tested in participants with mild cognitive impairment or Alzheimer's disease (NCT ...

9. mdpi.com mdpi.com/1424-8247/17/4/408

Nucleoside Reverse Transcriptase Inhibitor Exposure Is ... Nucleoside Reverse Transcriptase Inhibitor Exposure Is Associated with Lower Alzheimer's Disease Risk: A Retrospective Cohort Proof-of-Concept ...