RESvEraTrol in Parkinson's Disease (RESET)

ConditionParkinson's Disease

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age55-85

SponsorGeorgetown University

About this trial

This is an exploratory phase 2a study to investigate two doses of resveratrol (JotrolTM) vs placebo in individuals diagnosed with Parkinson's Disease (PD). Participants (n=30) will be randomized 1:1:1 into 3 groups and will receive oral JotrolTM vs placebo. Study drug will be titrated to reach a final maximal dose per group and will be administered orally once daily (QD) for 3 months. The study will primarily evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics (PK/PD) of JotrolTM.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Capable of providing informed consent (IC) and complying with study procedures

Stable on Levodopa and/or DA agonists for at least 4 weeks before enrollment

Clinical diagnosis of PD according to UK Brain Bank criteria and/or PD with Dementia (PDD) by MDS criteria (53-55).

MoCA≥18.

Disqualifiers

Known PD-linked gene mutations e.g. PINK-1, DJ-1, parkin, LRRK2 etc.

Clinical signs indicating syndromes or disorders other than PD including, Alzheimer's Disease (AD), corticobasal degeneration (CBD), supranuclear gaze palsy, multiple system atrophy (MSA), chronic traumatic encephalopathy (CTE), frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement

Any psychiatric diagnosis or symptoms, (e.g., hallucinations and suicidality, major depression, or delusions) that could interfere with study procedures

Medical history of liver or pancreatic disease, GI, ulcers and Chron's disease, kidney, or blood problems. Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG at Screening or Baseline. Any other medical conditions (e.g., cardiac, respiratory, GI, renal disease) which are not adequately controlled, or which in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments and are below grade 3 criteria as outlined in table 2.

Trial design

Design model

Parallel

Treatments tested in this trial

Trans-Resveratrol
Drug
Resveratrol (RSV) - or Trans-resveratrol- is polyphenolic compound in many plants, including grape, peanut, and berries. Biologically, RSV is a Sirtuin (SIRT) 1 activator that stimulates mitochondrial biogenesis; and regulates mitochondrial dynamics via autophagy (referred to as mitophagy). RSV plays a role in parkin-related mitophagy, which is necessary for mitochondrial dynamics but it is deficient in neurodegenerative diseases, including PD. RSV inhibits the activation of the NLRP3 (nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome, thereby lowering inflammation. The parallel roles of RSV to inhibit the NLRP3 inflammasome, increase autophagy and maintain mitochondrial integrity indicate that RSV is a therapeutic candidate that has strong neuroprotective effects via autophagy and inhibition of the NLRP3 inflammasome.

Treatment groups

30 Participants

are divided into 3 treatment groups

Group A: PlaceboPlacebo comparator 1 intervention

Group B: 200mg JotrolTMExperimental treatment 1 intervention

Group C: 400mg JotrolTMExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Evaluate the safety and tolerability of JotrolTM in individuals diagnosed with PD via Adverse Events (AEs) and Treatment Emergent AEs (TEAEs)

Time frame

12 weeks

Incidence of abnormal Electrocardiogram (ECG) findings [Safety and Tolerability])

Evaluate the safety and tolerability of JotrolTM in individuals diagnosed with PD via Electrocardiograms (ECG). ECGs with a QTc ≥500 ms and/or an increase of QTc ≥60 ms from baseline.

Time frame

Change from Baseline to Week-12

Determination of Jotrol's safe and tolerable dose in plasma [Safety and Tolerability]

Evaluate the PK of JotrolTM via measurement of its maximum concentration (Cmax) in plasma validated by the Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method

Time frame

Between 5 to 12 weeks

Determination of Jotrol's safe and tolerable dose in Cerebral Spinal Fluid (CSF) [Safety and Tolerability]

Evaluate the PK of JotrolTM via measurement of its maximum concentration (Cmax) in CSF validated by the Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method

Time frame

Between 5 to 12 weeks

Secondary outcomes

Energy metabolism via blood levels of ATP

Evaluate the effects of JotrolTM energy metabolism via blood levels of ATP

Time frame

Change from Baseline to Week-12

Plasma biomarker analysis for the inflammatory profile

Evaluate the effects of JotrolTM in plasma on markers of inflammation, including but not limited to Triggering Receptor Expressed on Myeloid Cells (TREM)-2, matrix metalloproteases (MMPs) interleukins (IL)- 1α\&β, 2, 3, 4, 5, 6, 7, 8 , 9, 10, 12, 13, 15, 17 α, chemokines (e.g. CXCL10, CCL2, CL7, CCL22, CCL3, CCL4), platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB, CCL5, CX3CL1, Tumor necrosis growth factor (TNF)-α, transforming growth factor (TGF)-α, and vascular endothelial growth factor (VEGF), neurofilaments, glial fibrillary acidic protein (GFAP).

Time frame

Change from Baseline to Week-12

Cerebral Spinal Fluid (CSF) biomarker analysis for the inflammatory profile

Evaluate the effects of JotrolTM in CSF on markers of inflammation, including but not limited to Triggering Receptor Expressed on Myeloid Cells (TREM)-2, matrix metalloproteases (MMPs) interleukins (IL)- 1α\&β, 2, 3, 4, 5, 6, 7, 8 , 9, 10, 12, 13, 15, 17 α, chemokines (e.g. CXCL10, CCL2, CL7, CCL22, CCL3, CCL4), platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB, CCL5, CX3CL1, Tumor necrosis growth factor (TNF)-α, transforming growth factor (TGF)-α, and vascular endothelial growth factor (VEGF), neurofilaments, glial fibrillary acidic protein (GFAP).

Time frame

Change from Baseline to Week-12

Other outcomes

Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-cog 14)

Evaluate the effects of JotrolTM on ADAS-cog 14 by measuring the change from Baseline to WK-12

Time frame

Change from Baseline to Week-12

Unified Parkinsons Disease Rating Scale Part 1, 2, and 3 (UPDRS 1, 2, and 3) (OFF)

Evaluate the effects of JotrolTM on UPDRS 1, 2, and 3 by measuring the change from Baseline to WK-12

Time frame

Change from Baseline to Week-12

Montreal Cognitive Assessment (MoCA)

Evaluate the effects of JotrolTM on MoCA by measuring the change from Baseline to WK-12

Time frame

Change from Baseline to Week-12

Neuropsychiatric Inventory (NIP)

Evaluate the effects of JotrolTM on NIP by measuring the change from Baseline to WK-12

Time frame

Change from Baseline to Week-12

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Georgetown University

Lead sponsor

Jupiter Neuroscience Inc.

Collaborator

Medstar Health Research Institute

Collaborator

Source ClinicalTrials.gov

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