Role of Pentoxifylline and Celecoxib in Parkinsonism

Phase 2

Recruiting

• Conditions: Parkinson Disease
• Interventions: Drug: carbidopa-levodopa; Drug: Pentoxifylline 400 MG; Drug: Celecoxib 200mg

• Registration Number: NCT05962957
• Lead Sponsor: Mostafa Bahaa

Brief Summary

Parkinson's disease (PD) is a chronic neurodegenerative disease clinically characterized by bradykinesia, hypokinesia, rigidity, resting tremor, and postural instability. These motor manifestations are attributed to the degeneration and selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), leading to a dopamine (DA) deficiency in the striatum.

The environmental factors are the most common risk factor for Parkinson's disease, while hereditary determinants have minor role for disease. Furthermore, the clinical diagnosis of PD rests on the identification of characteristics related to dopamine deficiency. However, nondopaminergic and nonmotor symptoms, including cognitive dysfunction and depression, which is one of the most common and persistent symptoms, are sometimes present at an earlier disease stage and, almost inevitably, emerge with the disease progression.

Neuroinflammation is considered one of the most important factors contributing critically to pathophysiology of PD . Recently, high mobility group box-1 (HMGB1) protein has been encoded as a potential inflammatory biomarker in PD. HMGB1 mediates immune response mostly through endothelial cells and macrophage activation via targeting two vital cell receptors; Toll-like receptor 4 (TLR4) and advanced glycation end products (RAGE). HMGB1 leads to a sequential cascade of inflammatory response through enhanced release of tumor necrosis factor-alpha (TNF-α) and interleukins (ILs), prominently IL-1β and IL-6. HMGB1 mediated also up-regulation of nuclear factor kappa-β (NF-κB) with subsequent flared pro-inflammatory storm.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-16
• Study First Submitted QC: 2023-07-25
• Study First Posted: 2023-07-27
• Study Start: 2023-08-07
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-16
• Last Update Posted: 2024-07-18
• Primary Completion: 2027-07-20
• Study Completion: 2028-10-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Age ≥ 18 years.
• Both male and female will be included.
• Patients diagnosed with PD according to Unified Parkinson's Disease Rating Scale.

Exclusion Criteria

• Breast feeding
• Patients with significant liver and kidney function abnormalities.
• Alcohol and / or drug abusers.
• Patients with known allergy to the study medications

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
control group	carbidopa-levodopa	control group ( levo-dopa group, n =25 ) who will receive levo-dopa/carbidopa (125/12.5) mg three times daily for 6 months.
PTX group	carbidopa-levodopa	(Pentoxyifylline group, n= 25) will receive levo-dopa/carbidopa (125/12.5) mg three times daily plus pentoxifylline 400 mg two times daily for 6 months.
PTX group	Pentoxifylline 400 MG	(Pentoxyifylline group, n= 25) will receive levo-dopa/carbidopa (125/12.5) mg three times daily plus pentoxifylline 400 mg two times daily for 6 months.
Celecoxib group	carbidopa-levodopa	will receive levo-dopa/carbidopa (125/12.5) mg three times daily plus celecoxib 200 mg once daily for 6 months.
Celecoxib group	Celecoxib 200mg	will receive levo-dopa/carbidopa (125/12.5) mg three times daily plus celecoxib 200 mg once daily for 6 months.

Primary Outcome Measures

Name	Time	Method
- Change From Baseline for Unified Parkinson's Disease Rating Scale (UPDRS) Total Score	6 months	- Change From Baseline for Unified Parkinson's Disease Rating Scale (UPDRS) Total Score (Time Frame: Baseline and week 24)

Trial Locations

Locations (1)

Faculty of Medicine, Mansoura University; 🇪🇬 Mansoura, Egypt