ALTO-100 for Bipolar Depression

Overseen By Alto Neuroscience

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alto Neuroscience

Must be taking: Mood stabilizers

Must not be taking: Prohibited medications

Disqualifiers: Unstable medical condition, Psychotic disorder, Substance use disorder, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 8

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of the new drug ALTO-100 as an additional treatment for individuals with bipolar disorder experiencing depression. Researchers will compare its effects to a placebo (a non-active pill) while participants continue their regular mood stabilizers. The trial seeks individuals diagnosed with Bipolar I or II who are currently experiencing a major depressive episode and have maintained a stable dose of mood stabilizers like lithium or lamotrigine for at least six weeks. Participants should be prepared to engage in all study activities and procedures. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to continue taking a mood stabilizer like lithium, lamotrigine, or valproic acid, without changing the dose for at least 6 weeks before starting. If you're on other medications, the protocol doesn't specify, so it's best to discuss with the trial team.

Is there any evidence suggesting that ALTO-100 is likely to be safe for humans?

Research has shown that ALTO-100 was safe and well-tolerated in earlier studies. Although ALTO-100 did not significantly improve symptoms of major depressive disorder (MDD), it maintained a positive safety profile. Most participants did not experience serious side effects. While it didn't achieve the primary goal of alleviating depression, the treatment was generally safe for study participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bipolar depression?

Researchers are excited about ALTO-100 for bipolar depression because it offers a potentially novel approach to treating this challenging condition. Unlike standard treatments, which often focus on mood stabilization through medications like lithium or atypical antipsychotics, ALTO-100 may work through a different mechanism, possibly providing relief for patients who do not respond well to existing options. Additionally, the twice-daily oral administration of ALTO-100 might offer a more convenient and consistent treatment regimen. This fresh angle on tackling bipolar depression could lead to more personalized and effective care for patients.

What evidence suggests that ALTO-100 might be an effective treatment for bipolar depression?

Research shows that ALTO-100 aims to help the brain grow and adapt by encouraging the creation of new brain cells and improving the brain's ability to change. This occurs through a process involving a protein that supports brain health. Although earlier studies in major depressive disorder found that ALTO-100 did not significantly reduce symptoms compared to a placebo, its unique way of enhancing brain function might still benefit bipolar depression, which has different causes. In this trial, participants will receive either ALTO-100 or a placebo to evaluate its effectiveness for bipolar depression. More research is needed to determine its efficacy for this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Mallory Loflin, PhD

Principal Investigator

Alto Neuroscience

Are You a Good Fit for This Trial?

This trial is for individuals with bipolar disorder (either type I or II) who are currently experiencing a major depressive episode. Participants must be on a mood stabilizer to join the study. Specific details about what excludes someone from participating aren't provided here.

Inclusion Criteria

Are you currently taking mood stabilizers, lithium, lamotrigine, valproic acid, or an atypical antipsychotic?

Are you taking a stable dose of any of the medications listed below for Bipolar? Lamotrigine, valproic acid, lamictal, olanzapine, quetiapine, lurasidone, risperidone, ziprasidone, cariprazine, aripiprazole, lumateperone, or asenapine

Exclusion Criteria

Have you been diagnosed with Schizophrenia?

Do you use any substances and/or street drugs including marijuana and alcohol?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blind Treatment

Participants receive either ALTO-100 or placebo adjunctively to a mood stabilizer for 6 weeks

6 weeks

4 visits (in-person)

Open-Label Treatment

Eligible participants receive ALTO-100 for up to 7 weeks

7 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALTO-100

Trial Overview The study is testing the effectiveness of ALTO-100 compared to a placebo in reducing symptoms of depression in bipolar disorder when taken alongside standard mood stabilizers. It includes an initial double-blind phase followed by an open label period where all participants know they're receiving ALTO-100.

How Is the Trial Designed?

Group I: ALTO-100 Experimental Treatment 1 Intervention

Participants will receive ALTO-100 40 mg tablet twice daily, from Day 1 to Week 6 in the double blind (DB) treatment period. Eligible participants who enter the open label (OL) treatment period will receive ALTO-100 40 mg tablet twice daily from OL baseline until the end of OL period/early termination visit (Up to 7 weeks).

Group II: Placebo DB Placebo Group 1 Intervention

Participants will receive matching placebo tablet twice daily, from Day 1 to Week 6 in the double blind (DB) treatment period.

Who Is Running the Clinical Trial?

Alto Neuroscience

Lead Sponsor

Trials

11

Recruited

1,300+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06656416

ALTO-100 in Bipolar Disorder With Depression (BD-D) The purpose of this study is to assess antidepressant efficacy differences between ALTO-100 and placebo during the Double-Blind period in patients with bipolar ...

2. investors.altoneuroscience.com investors.altoneuroscience.com/news/news-details/2024/Alto-Neuroscience-Reports-Topline-Results-from-a-Phase-2b-Trial-Evaluating-ALTO-100-as-a-Treatment-for-Major-Depressive-Disorder/default.aspx

Alto Neuroscience Reports Topline Results from a Phase ... Treatment with ALTO-100 did not demonstrate improvement in depressive symptoms compared to placebo in patients with a memory-based cognitive biomarker.

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/phase-iib-alto-100-fails-primary-endpoint/

Alto's Phase IIb study of ALTO-100 fails to meet primary ... Alto Neuroscience (Alto) has reported that its Phase IIb clinical trial of ALTO-100 for treating MDD failed to meet its primary endpoint.

4. firstwordpharma.com firstwordpharma.com/story/5961081

Alto Neuroscience Reports First Quarter 2025 Financial ... ALTO-100: Enrollment ongoing in Phase 2b bipolar depression trial; data expected in the second half of 2026. ALTO-100, a first-in-class ...

5. cirm.ca.gov cirm.ca.gov/our-progress/awards/phase-2b-study-efficacy-novel-pro-neurogenesis-pro-plasticity-drug-bipolar-depression-using-precision-psychiatry-approach/

A Phase 2b Study of the Efficacy of a Novel Pro-Neurogenesis ... ALTO-100 increased hippocampal neurogenesis and neuroplasticity. Its effects are mediated by signaling through the brain derived neurotrophic factor (BDNF) ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/549400

ALTO-100 in Bipolar Disorder With Depression (BD-D) The purpose of this study is to assess antidepressant efficacy differences between ALTO-100 and placebo during the Double-Blind period in ...

7. psychiatrictimes.com psychiatrictimes.com/view/disappointing-phase-2b-results-for-alto-100-for-mdd-precision-medicine

Disappointing Phase 2b Results for ALTO-100 for MDD, ... Although safety and tolerability was positive, ALTO-100 failed to reach primary endpoint in MDD study.