Allopregnanolone As a Regenerative Treatment for Parkinson's Disease

NCT ID: NCT06263010

Last Updated: 2024-10-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-12
• Study Completion Date: 2025-05-31

Brief Summary

The goal of this open-label, pilot clinical trial is to test allopregnanolone as a regenerative treatment in patients with Parkinson's disease (PD). The main questions this study aims to answer are:

1. Is a large-scale clinical trial testing how well it works in patients with PD feasible?

2. Is allopregnanolone safe and well-tolerated in patients with PD.

3. Can we see any signals of changes in imaging and clinical scales?

Participants will receive a weekly infusion in their vein of allopregnanolone for a total of 12 weeks. There is no placebo so everyone receives allopregnanolone and "Open-label" means the study is not blinded so both the participant and investigators know the assigned treatment.

Detailed Description

This is an open-label, pilot clinical trial of allopregnanolone (Allo) as a regenerative treatment for Parkinson's disease. A total of 10 study participants will receive weekly infusions of Allo for 12 weeks. Participants will be male and female, age 40-80 years with a history of idiopathic, sporadic PD who have a Hoehn & Yahr stage 1-4. Allo is a potent neuroregenerative agent that promotes proliferation of human neural stem cells and has the potential to function as a regenerative therapeutic to restore motor function in persons with PD. Results from several preclinical studies in rodent models of PD confirm improved motor function after Allo treatment.

Primary Objective: To assess the feasibility of a large-scale trial to determine the efficacy of weekly infusions of Allo in in patients with Idiopathic sporadic PD.

Secondary Objectives: To evaluate the safety and tolerability of weekly infusions of Allo in participants with idiopathic sporadic PD, and assess single-dose pharmacokinetics of allopregnanolone.

Tertiary / Exploratory Objectives: To assess efficacy signals of weekly infusions of Allo in participants with idiopathic sporadic PD.

• Determine target engagement of Allo using dopamine transporter (DaT) imaging and magnetic resonance imaging (MRI).
• Evaluate effect of Allo on motor function tests.
• Evaluate the effect of Allo on cognitive function tests and clinical ratings.
• Compare response to Allo administration between APOE4 carriers and non-carriers.

Conditions

Parkinson Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Allo APOE4 carriers

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 Type: EXPERIMENTAL

Allopregnanolone

Intervention Type: DRUG

Allopregnanolone is a neurosteroid ( 3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) and by-product of the metabolism of the hormone progesterone.

Allo APOE4 none-carriers

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.

Group Type: ACTIVE_COMPARATOR

Allopregnanolone

Intervention Type: DRUG

Allopregnanolone is a neurosteroid ( 3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) and by-product of the metabolism of the hormone progesterone.

Interventions

Allopregnanolone

Allopregnanolone is a neurosteroid ( 3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) and by-product of the metabolism of the hormone progesterone.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• History of Idiopathic sporadic Parkinson disease
• Hoehn & Yahr stage 1-4
• Have been on stable doses of all anti-Parkinson's medications for 30 days prior to screening
• Provision of signed and dated informed consent form

Exclusion Criteria

• Evidence of Parkinsonian syndrome.
• Any conditions that would contraindicate MRI studies.
• Undergone deep brain stimulation (DBS) surgery as treatment for PD.
• 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.
• History within the last 5 years of a primary or recurrent malignant disease, with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or prostate cancer in situ with a post-treatment prostatic-specific antigen within normal range.
• Serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than PD), psychiatric, immunologic, or hematologic disease, and any other conditions that, in the investigator's opinion, could interfere with the safety and efficacy analyses in this study.
• History of chronic alcohol or substance abuse/dependence within the past 3 years.
• Current use of benzodiazepines, anticonvulsants, antipsychotics, or other drugs that might interact with the gamma-aminobutyric acid-A (GABA-A) receptor complex; use of calcium-channel blockers (e.g., amlodipine); use of dietary supplements containing Pregnenolone.
• Treatment with another investigational drug within 3 months of screening.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roberta Brinton

OTHER

Sponsor Role: lead

Responsible Party

Roberta Brinton

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Scott Sherman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Roberta D Brinton, PhD

Role: STUDY_CHAIR

University of Arizona

Gerson D Hernandez, MD, MPH

Role: STUDY_DIRECTOR

University of Arizona

Locations

The University of Arizona Clinical & Translational Science Research Center

Tucson, Arizona, United States

Countries

United States

Other Identifiers

CIBS-2023-01

Identifier Type: -

Identifier Source: org_study_id