Pentoxifylline and Parkinsonism

Study Overview
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Brief Summary
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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.

Official Title
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Clinical Study to Compare the Possible Safety and Efficacy of Pentoxifylline in Patients With Parkinson's Disease Treated With Conventional Treatment

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: carbidopa-levodopa
* Drug: Pentoxifylline 400 MG


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: control group<br>control group ( levo-dopa group, n =25 ) who will receive levo-dopa/carbidopa (125/12.5) mg three times daily for 6 months. | Drug: carbidopa-levodopa<br>* 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<br>|
| Active Comparator: PTX group<br>(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. | Drug: carbidopa-levodopa<br>* 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<br>Drug: Pentoxifylline 400 MG<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

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