Allopregnanolone for Parkinson's Disease

(Allo-PD Trial)

Overseen By Claudia M Lopez, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roberta Brinton

Must be taking: Anti-Parkinson's

Must not be taking: Benzodiazepines, Anticonvulsants, Antipsychotics, others

Disqualifiers: Deep brain stimulation, Malignant disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests allopregnanolone, a potential new treatment for Parkinson's disease. Researchers aim to determine its safety, tolerability, and any indications of benefit based on brain imaging and clinical observations. Every participant receives the treatment, with no placebo involved. Individuals with idiopathic sporadic Parkinson's, who have maintained stable medication for at least 30 days, may qualify for this trial. 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?

You need to be on stable doses of all anti-Parkinson's medications for at least 30 days before joining the trial. However, you cannot use benzodiazepines, anticonvulsants, antipsychotics, calcium-channel blockers, or supplements with Pregnenolone.

Is there any evidence suggesting that allopregnanolone is safe for humans?

Research has shown that allopregnanolone has been studied for safety in humans. In past studies, participants received allopregnanolone in a controlled environment, and researchers monitored for side effects. The treatment was generally well-tolerated. Some participants experienced mild side effects, such as dizziness or headaches, but these were not serious.

Allopregnanolone has also been tested for other conditions, such as Alzheimer's disease. In these studies, it appeared to support brain health and reduce inflammation. Importantly, no major safety issues emerged, suggesting it could be safe for use in Parkinson's disease as well.

Since this trial is in an early phase, the treatment undergoes careful safety testing. Early-phase trials primarily focus on ensuring a treatment's safety. So far, allopregnanolone seems to meet this goal, but ongoing studies will provide more information. ^{1 2 3 4 5}

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

Researchers are excited about using allopregnanolone for Parkinson's disease because it offers a novel approach compared to the current standard treatments like Levodopa and dopamine agonists. Allopregnanolone is a neurosteroid that may protect brain cells and promote brain health by enhancing neurogenesis and modulating inflammation, unlike existing treatments that primarily focus on replenishing dopamine levels. Additionally, its method of delivery via weekly intravenous infusion could provide a consistent and controlled dosage, potentially leading to more stable and lasting effects. This new mechanism and delivery method could offer hope for improved management of Parkinson's symptoms and disease progression.

What evidence suggests that allopregnanolone might be an effective treatment for Parkinson's disease?

Research has shown that allopregnanolone could be a promising treatment for Parkinson's disease. In animal studies, it improved movement, a major challenge for people with Parkinson's. Specifically, it reduced cognitive problems in a particular rat model of the disease, suggesting it might help with both movement and cognitive issues in humans. Although human research remains in the early stages, these findings offer hope for its potential benefits. Participants in this trial will receive allopregnanolone, with separate groups for APOE4 gene carriers and non-carriers, to further explore its effects. ^{1 2 3 6 7}

Who Is on the Research Team?

Gerson D Hernandez, MD, MPH

Principal Investigator

University of Arizona

Scott Sherman, MD

Principal Investigator

University of Arizona

Roberta D Brinton, PhD

Principal Investigator

University of Arizona

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's Disease. Participants will receive weekly infusions of allopregnanolone over 12 weeks. There are specific inclusion and exclusion criteria, but they're not listed here.

Inclusion Criteria

I have been diagnosed with Parkinson's disease without a known cause.

Provision of signed and dated informed consent form

My Parkinson's medication doses have been stable for the last 30 days.

Exclusion Criteria

Iodine allergy, known serious hypersensitivity to ioflupane I-123, or other inability to undergo DaTscan

Clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness

I have had DBS surgery for Parkinson's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly infusions of allopregnanolone for 12 weeks

12 weeks

12 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

• Allopregnanolone

Trial Overview The study tests allopregnanolone as a potential regenerative treatment for Parkinson's Disease. It aims to determine the feasibility of a larger trial, assess safety and tolerability, and look for any positive changes in brain imaging and clinical assessments.

How Is the Trial Designed?

Group I: Allo APOE4 carriers Experimental Treatment 1 Intervention

Group of 5 participants who are carriers of the APOE4 gene and will receive allopregnanolone 4mg administered weekly via a 30-min IV infusion for a duration of 12 weeks.

Group II: Allo APOE4 none-carriers Active Control 1 Intervention

Group of 5 participants who are none-carriers of the APOE4 gene and will receive allopregnanolone 4mg administered weekly via a 30-min IV infusion for a duration of 12 weeks.

Allopregnanolone is already approved in United States for the following indications:

Approved in United States as Zulresso for:

• Postpartum depression

Who Is Running the Clinical Trial?

Roberta Brinton

Lead Sponsor

Trials

2

Recruited

110+

Citations

1. clinicaltrial.be clinicaltrial.be/en/details/425792?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Allopregnanolone As a Regenerative Treatment for ... Results from several preclinical studies in rodent models of PD confirm improved motor function after Allo treatment. Primary Objective: To ...

2. ctv.veeva.com ctv.veeva.com/study/allopregnanolone-as-a-regenerative-treatment-for-parkinsons-disease

Allopregnanolone As a Regenerative Treatment for ... The goal of this open-label, pilot clinical trial is to test allopregnanolone as a regenerative treatment in patients with Parkinson's disease (PD).

3. withpower.com withpower.com/trial/phase-1-parkinson-disease-2024-af07f

Allopregnanolone for Parkinson's Disease (Allo-PD Trial) The goal of this open-label, pilot clinical trial is to test allopregnanolone as a regenerative treatment in patients with Parkinson's disease (PD).

4. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06263010/

Trial | NCT06263010 The goal of this open-label, pilot clinical trial is to test allopregnanolone as a regenerative treatment in patients with Parkinson's disease (PD).

5. sciencedirect.com sciencedirect.com/science/article/pii/S0149763424001374

Allopregnanolone and its antagonist modulate ... Neurosteroid allopregnanolone attenuates cognitive dysfunctions in 6-OHDA-induced rat model of Parkinson's disease. Behav. Brain Res., 305 (2016), pp. 258 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10124616/

Allopregnanolone as regenerative therapeutic for Alzheimer's ... With an optimized dosing and treatment regimen, chronic allopregnanolone administration promoted neurogenesis, oligodendrogenesis, reduced neuroinflammation and ...

7. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Allopregnanolone_UPDATE.pdf

Allopregnanolone The phase 1b/2a was a safety study (data discussed in the “Safety” section). Exploratory endpoints included cognitive and MRI outcomes, but the studies were not.