Role of Pentoxifylline and Celecoxib in Parkinsonism

Mostafa Bahaa

Status and phase: Completed; Phase 2

Conditions: Parkinson Disease

Treatments: Drug: Pentoxifylline 400 MG; Drug: Celecoxib 200mg; Drug: carbidopa-levodopa

Study type: Interventional

Funder types: Other

Identifiers

NCT05962957

1235

Details and patient eligibility

About

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.

Enrollment: 80 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 3 patient groups

control group

Active Comparator group

Description:

control group ( levo-dopa group, n =25 ) who will receive levo-dopa/carbidopa (125/12.5) mg three times daily for 6 months.

Treatment:

Drug: carbidopa-levodopa

PTX group

Active Comparator group

Description:

(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.

Treatment:

Drug: carbidopa-levodopa

Drug: Pentoxifylline 400 MG

Celecoxib group

Active Comparator group

Description:

will receive levo-dopa/carbidopa (125/12.5) mg three times daily plus celecoxib 200 mg once daily for 6 months.

Treatment:

Drug: carbidopa-levodopa

Drug: Celecoxib 200mg