Role of Pentoxifylline and Celecoxib in Parkinsonism

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.

Conditions

• Parkinson Disease

Interventions

DRUG

carbidopa-levodopa

Levodopa is typically prescribed to a patient with Parkinson disease once symptoms become more difficult to control with other anti-parkinsonism drugs. The drug can also be used for postencephalitic parkinsonism and symptomatic parkinsonism due to carbon monoxide intoxication

DRUG

Pentoxifylline 400 MG

Pentoxifylline (PTX) has a well validated immune modulatory and anti-inflammatory efficacy via suppression of the TLR4/NF-κB network signaling pathway. Moreover, Pentoxifylline has a potential antioxidant capacity mostly via nuclear erythroid 2-related factor 2 (Nrf2) activation with subsequent up-regulation and expression of several antioxidant enzymes

DRUG

Celecoxib 200mg

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate pain and help relieve symptoms of arthritis

Sponsors & Collaborators

• Tanta University

  collaborator OTHER

• Mohanad Omar Khrieba Clinical Pharmacy Department, Faculty of Pharmacy - Horus University

  collaborator UNKNOWN

• Mostafa Bahaa

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-08-07

Primary Completion

2024-09-20

Completion

2024-09-20

Countries

• Egypt

Study Locations