Pentoxifylline and Parkinsonism

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

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: carbidopa-levodopa; Drug: Pentoxifylline 400 MG

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Mansoura, Egypt, 35511
    • Recruiting
    • Faculty of Medicine, Mansoura University
    • Contact: Mostafa M Bahaa, PhD; Phone Number: 0201025538337; Email: mbahaa@horus.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: control group; 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; 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
Active Comparator: PTX group; (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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mostafa Bahaa
• Collaborators: Sahar Mohamed El-Haggar clinical pharmacy department, Tanta University; Sahar Kamal Hegazi clinical pharmacy department, Tanta University; Mohanad Omar Khrieba Clinical Pharmacy Department, Faculty of Pharmacy - Horus University

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Estimated): July 20, 2027
• Study Completion (Estimated): October 20, 2028

Study Registration Dates

• First Submitted: July 16, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Immunologic Factors; Protective Agents; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Carbidopa, levodopa drug combination; Pentoxifylline
• Other Study ID Numbers: 1235

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No