Disease-modifying Efficacy of Sitagliptin Therapy in Early-stage Parkinson's Disease

Inclusion criteria

• Male or female participants aged 50 to 80 years, inclusive.
• Participants diagnosed with Clinically Established Parkinson's Disease or Clinically Probable Parkinson's Disease according to the Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's Disease (Postuma et al., 2015).
• Participants diagnosed with Parkinson's disease within 3 years prior to screening.
• Participants who are either treatment-naïve to antiparkinsonian medications at screening or receiving stable levodopa monotherapy, defined as maintenance of the same levodopa dose for at least 12 weeks immediately prior to screening without concomitant use of other antiparkinsonian medications.
• Hoehn and Yahr stage 1 or 2 in the ON state.
• Participants with documented evidence, based on ¹⁸F-FP-CIT PET performed at the investigational site within 36 months prior to screening, of reduced dopamine transporter (DAT) availability in the posterior putamen. Raw DICOM files must be retrievable and suitable for quantitative analysis of standardized uptake value ratio (SUVR) or specific binding ratio (SBR) by the central reader. Participants without an available prior ¹⁸F-FP-CIT PET result must agree to undergo an additional ¹⁸F-FP-CIT PET scan.
• Participants with documented brain MRI performed at any time prior to screening or during the screening period, confirming exclusion of causes other than Parkinson's disease, including atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), cerebrovascular disease, normal-pressure hydrocephalus, and brain tumor. The T1-weighted sequence must be suitable for comparison with the follow-up MRI performed at Visit 9.
• Mini-Mental State Examination (MMSE) score ≥24, to exclude severe cognitive impairment.
• Participants who understand the clinical trial protocol and voluntarily provide written informed consent.
• Participants who are able and willing to comply with follow-up visits and study assessments throughout the entire study period.

Exclusion criteria

• Participants with suspected atypical parkinsonian syndromes, including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), or other atypical parkinsonian disorders.
• Participants with vascular parkinsonism, drug-induced parkinsonism, or toxin-induced parkinsonism.
• Participants with secondary parkinsonism due to causes such as normal-pressure hydrocephalus, brain tumor, or other identifiable secondary causes.
• Participants currently receiving dopaminergic medications other than levodopa, including dopamine agonists, monoamine oxidase-B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, amantadine, or other antiparkinsonian medications.
• Participants with levodopa-induced motor fluctuations or levodopa-induced dyskinesia (LID) that interfere with activities of daily living, defined as a score of ≥2 on MDS-UPDRS Part IV Item 4.1 or 4.2.
• History of hypersensitivity to sitagliptin or any other dipeptidyl peptidase-4 (DPP-4) inhibitor.
• Current treatment with a DPP-4 inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist.
• History of acute or chronic pancreatitis.
• Acute cholecystitis or cholangitis.
• Participants with previously diagnosed diabetes mellitus who are currently receiving antidiabetic medication.However, participants with a diagnosis of diabetes mellitus who are not currently receiving antidiabetic medication, or those found to have HbA1c ≥6.5% during screening, may be enrolled. Participants with HbA1c ≥7.5% will be excluded because combination antidiabetic therapy may be required.
• Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m², indicating moderate or greater renal impairment.
• Hepatic dysfunction, defined as AST or ALT >3 times the upper limit of normal (ULN).
• Pancreatic enzyme abnormality, defined as amylase or lipase >3 times the ULN.
• Clinically significant cardiovascular disease, including New York Heart Association (NYHA) Class III-IV heart failure, myocardial infarction, or stroke within 6 months prior to screening.
• History of malignancy within 5 years prior to screening, except for completely treated non-melanoma skin cancer.
• Uncontrolled, clinically significant psychiatric disorder.
• Participants who are pregnant or breastfeeding, or women of childbearing potential who are unwilling or unable to use an appropriate method of contraception.
• Participation in another clinical trial within 30 days prior to screening.
• Participants considered unsuitable for participation in the clinical trial based on the investigator's clinical judgment.