Clinical trial NCT06263010: Allopregnanolone As a Regenerative Treatment for Parkinson's Disease
Official title: Allopregnanolone As a Regenerative Treatment for Parkinson's Disease: an Open-label, Pilot Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Parkinson Disease
Keywords: Parkinson
Allopregnanolone
Regenerative therapeutic
Lead sponsor: University of Arizona
Sponsor class: OTHER
First posted: 2024-02-16
Enrollment: 10
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Study completion
timeFrame: Week 13
Secondary outcomes:
measure: Adverse Events
timeFrame: Weekly from Baseline to Week 16
measure: Infusion Reactions
timeFrame: Weekly from Week 1 to Week 16
measure: Pharmacokinetics: Peak Plasma Concentration (Cmax)
timeFrame: Week 1
measure: Pharmacokinetics: Time of peak concentration (tmax)
timeFrame: Week 1
measure: Pharmacokinetics: Half-life (t1/2)
timeFrame: Week 1
measure: Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)
timeFrame: Week 1
Other outcomes:
measure: Dopamine transporter (DaT) SPECT imaging
timeFrame: Baseline to week 13
measure: MRI: Regional brain volumes
timeFrame: Screening to week 13
measure: MRI: Fractional Anisotropy
timeFrame: Screening to week 13
measure: MRI: Quantitative anisotropy
timeFrame: Screening to week 13
measure: MRI: Functional connectivity
timeFrame: Screening to week 13
measure: Mean rate of change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score part I (non-motor EDL)
timeFrame: Baseline to week 13
measure: Mean rate of change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score part II (motor EDL)
timeFrame: Baseline to week 13
measure: Mean rate of change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score part III (motor examination)
timeFrame: Baseline to week 13
measure: Mean rate of change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score part IV (motor complications)
timeFrame: Baseline to week 13
measure: Mean rate of change in the Unified Dyskinesia Rating Scale (UDysRS) total score
timeFrame: Baseline to week 13
measure: Change from baseline in Montreal Cognitive Assessment (MoCA) score
timeFrame: Baseline to week 13
measure: Change from baseline in Parkinson's disease Questionnaire (PDQ-39).
timeFrame: Baseline to week 13
measure: Change from baseline in Hamilton Depression Rating Scale (HAM-D)
timeFrame: Baseline to week 13
measure: Cambridge Cognition's Paired Associates Learning (PAL) Test
timeFrame: Baseline to week 13
measure: Cambridge Cognition's Motor Screening Task (MOT)
timeFrame: Baseline to week 13
measure: Cambridge Cognition's One Touch Stockings of Cambridge (OTS)
timeFrame: Baseline to week 13
Locations:
city: Tucson
country: United States
facility: The University of Arizona Clinical & Translational Science Research Center
state: Arizona
Study officials:
affiliation: University of Arizona
name: Scott Sherman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Arizona
name: Roberta D Brinton, PhD
role: STUDY_CHAIR
affiliation: University of Arizona
name: Gerson D Hernandez, MD, MPH
role: STUDY_DIRECTOR
References: