Clinical trial NCT06928519: Efficacy and Safety of Entacapone Combined With Madopar in the Treatment of Early Parkinson's Disease: An Observational, Multicenter, Case-Control Study
Official title: Efficacy and Safety of Entacapone Combined With Madopar in the Treatment of Early Parkinson's Disease: An Observational, Multicenter, Case-Control Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Parkinson Disease (PD)
Keywords: Parkinson Disease
Levodopa
Benserazide
Entacapone
Lead sponsor: Guangxi Medical University
Sponsor class: OTHER
Collaborators: name: Jiangbin Hospital of Guangxi Zhuang Autonomous Region
name: Guangxi International Zhuang Medicine Hospital
name: Ethnic Hospital of Guangxi Zhuang Autonomous Region
name: Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University
First posted: 2025-04-15
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will enroll adult patients diagnosed with Parkinson's disease according to MDS criteria, aged between 18 and 80 years, and in the early stages of the disease (modified Hoehn-Yahr stage 1-2.5). Participants must have a Mini-Mental State Examination (MMSE) score ≥26 and a Beck Depression Inventory (BDI) score \<15. Eligible patients will include those who are either levodopa-naïve or have been on a stable dose of levodopa (300-600 mg/day) for at least one month. All participants must voluntarily agree to join the study, provide informed consent, and be able to comply with the study protocol.

Brief summary: This observational, multicenter, case-control study aims to evaluate the efficacy and safety of Entacapone combined with Madopar (levodopa/benserazide) in the treatment of early-stage Parkinson's disease (PD) among Chinese patients. The study will enroll patients diagnosed with PD according to the MDS criteria, aged 18-80, with modified Hoehn-Yahr stages 1-2.5, and who have not previously used Entacapone. Participants will be assigned to two groups based on their prior treatment history: the LBE group (levodopa/benserazide/entacapone) or the LB group (levodopa/benserazide only), according to their actual clinical treatment plan.

The study will observe patients over a 24-week period, evaluating changes in motor symptoms using the MDS-UPDRS Part III score as the primary endpoint. Secondary outcomes include assessments of daily living abilities, motor complications, quality of life (PDQ-39), cognitive function (MMSE), global impression (CGI), and safety profiles, including adverse event reporting.

This study does not involve any interventional treatment changes; all therapeutic decisions remain at the discretion of the treating physicians. The findings are expected to provide real-world evidence regarding the potential benefits and safety of adding Entacapone to Madopar in the management of early PD.

Detailed description: This is an observational, multicenter, case-control study designed to evaluate the efficacy and safety of Entacapone combined with Madopar (Levodopa/Benserazide, LB) in the treatment of early-stage Parkinson's disease (PD) in Chinese patients. The study is conducted across multiple centers in China and includes patients diagnosed with PD according to the MDS criteria, aged 18-80 years, with a modified Hoehn-Yahr stage of 1-2.5. Participants will be divided into two groups based on their actual clinical treatment: (1) the LBE group (Levodopa/Benserazide/Entacapone) and (2) the LB group (Levodopa/Benserazide only). The study does not involve any randomization, blinding, or intervention allocation; instead, it reflects real-world clinical practice, where all treatment decisions are made solely by the attending physician.

The study will observe patients over a 24-week period to compare the effectiveness of the two treatment strategies in improving motor symptoms, daily living activities, and quality of life, as well as the incidence of adverse events. The primary outcome measure is the change in MDS-UPDRS Part III (motor examination) score from baseline to Week 24. Secondary outcomes include changes in MDS-UPDRS Part II (activities of daily living), Part IV (motor complications), total MDS-UPDRS II+III scores, PDQ-39 quality of life scores, Clinical Global Impression (CGI) scores, MMSE cognitive scores, and modified Hoehn-Yahr staging. Safety assessments include adverse events, serious adverse events, vital signs, laboratory tests, and ECG findings.

All treatments, including medication selection, dosage, and adjustment, will follow the treating physician's routine clinical judgment, and no intervention or modification by the study team will occur. Concomitant medications such as amantadine, anticholinergics, dopamine agonists, and MAO-B inhibitors (e.g., selegiline, rasagiline) are allowed if their doses are stable for at least 30 days before enrollment and remain unchanged throughout the study period.

The estimated sample size is 216 participants, with approximately 108 in each group, allowing for a 10% dropout rate. The study is expected to start in June 2025 and complete by April 2027, with final data analysis by June 2027. The results of this study aim to provide real-world evidence regarding the potential benefits and safety of Entacapone combined with Madopar in the early-stage PD population in China.

Eligibility criteria: Inclusion Criteria:

Age between 18 and 80 years;

Diagnosed with Parkinson's Disease based on the MDS criteria, confirmed by a movement disorder neurologist;

Modified Hoehn and Yahr stage between 1 and 2.5;

No prior use of entacapone;

MMSE score ≥ 26;

BDI (Beck Depression Inventory) score \< 15;

Either:

Has never used levodopa before, or

Has been on a stable dose of levodopa (300-600 mg/day) for at least 1 month prior to enrollment;

Stable doses of amantadine, anticholinergics, dopamine agonists, selegiline, or rasagiline are allowed if maintained for at least 30 days prior to and during the study;

Willing and able to give informed consent and comply with study procedures, with caregiver support if needed.

Exclusion Criteria:

Previous use of entacapone or tolcapone for more than 30 days, or within 4 weeks before baseline;

Use of dopamine agonists within 4 weeks before baseline;

BDI score ≥ 15;

MMSE score \< 26;

Unstable levodopa dosage;

History of dyskinesia;

Diagnosis of atypical or secondary parkinsonism, or history of PD-related neurosurgery;

Clinically significant medical conditions within the past 5 years that could interfere with study participation;

Use of medications known to induce parkinsonism;

Participation in other investigational drug trials within 30 days before baseline.

Primary outcomes:
measure: Change from baseline to Week 24 in the MDS-UPDRS Part III (Motor Examination) score
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change from baseline to Week 24 in the MDS-UPDRS Parts II and III total score
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in the MDS-UPDRS Part II (Activities of Daily Living) score
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in the MDS-UPDRS Part IV score
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in the PDQ-39 summary index score
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in the Clinical Global Impression (CGI) score
timeFrame: Baseline to Week 24
measure: Change in modified Hoehn-Yahr stage from baseline to Week 24
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guanxi
Study officials:
References:
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citation: Fung VS, Herawati L, Wan Y; Movement Disorder Society of Australia Clinical Research and Trials Group; QUEST-AP Study Group. Quality of life in early Parkinson's disease treated with levodopa/carbidopa/entacapone. Mov Disord. 2009 Jan 15;24(1):25-31. doi: 10.1002/mds.21878.
citation: Lew MF, Somogyi M, McCague K, Welsh M; Lce QoL Study Group. Immediate versus delayed switch from levodopa/carbidopa to levodopa/carbidopa/entacapone: effects on motor function and quality of life in patients with Parkinson's disease with end-of-dose wearing off. Int J Neurosci. 2011 Nov;121(11):605-13. doi: 10.3109/00207454.2011.598982. Epub 2011 Aug 16.
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citation: Hauser RA, Panisset M, Abbruzzese G, Mancione L, Dronamraju N, Kakarieka A; FIRST-STEP Study Group. Double-blind trial of levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson's disease. Mov Disord. 2009 Mar 15;24(4):541-50. doi: 10.1002/mds.22343.
citation: Liao X, Wu N, Liu D, Shuai B, Li S, Li K. Levodopa/carbidopa/entacapone for the treatment of early Parkinson's disease: a meta-analysis. Neurol Sci. 2020 Aug;41(8):2045-2054. doi: 10.1007/s10072-020-04303-x. Epub 2020 Mar 11.
citation: Kuoppamaki M, Leinonen M, Poewe W. Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson's disease patients with wearing-off. J Neural Transm (Vienna). 2015 Dec;122(12):1709-14. doi: 10.1007/s00702-015-1449-6. Epub 2015 Sep 7.