Role of Pentoxifylline and Celecoxib in Parkinsonism

NCT05962957 | Completed Phase 2

• 1 other identifier: 1235
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• - 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

Study Arms (3)

control group

ACTIVE COMPARATOR

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

PTX group

ACTIVE COMPARATOR

(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; Drug: Pentoxifylline 400 MG

Celecoxib group

ACTIVE COMPARATOR

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

Drug: carbidopa-levodopa; Drug: Celecoxib 200mg

Interventions

carbidopa-levodopa DRUG

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

Celecoxib group; PTX group; control group

Pentoxifylline 400 MG DRUG

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

PTX group

Celecoxib 200mg DRUG

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

Celecoxib group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Mostafa Bahaa: lead
• Tanta University: collaborator
• Mohanad Omar Khrieba Clinical Pharmacy Department, Faculty of Pharmacy - Horus University: collaborator

Study Sites (1)

Faculty of Medicine, Mansoura University

Al Mansurah, 35511, Egypt

Location

Related Publications (2)

• Khrieba MO, Hegazy SK, Mohammed WF, El-Haggar SM. Clinical study to investigate the adjuvant role of Pentoxifylline in patients with Parkinson's disease: A randomized controlled study. Int Immunopharmacol. 2025 May 27;156:114689. doi: 10.1016/j.intimp.2025.114689. Epub 2025 Apr 19.

  PMID: 40253769 DERIVED

• Khrieba MO, Hegazy SK, Mustafa W, El-Haggar SM. Repurposing celecoxib as adjuvant therapy in patients with Parkinsonian disease: a new therapeutic dawn: randomized controlled pilot study. Inflammopharmacology. 2024 Dec;32(6):3729-3738. doi: 10.1007/s10787-024-01567-z. Epub 2024 Sep 28.

  PMID: 39340691 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

carbidopa, levodopa drug combination; Pentoxifylline; Celecoxib

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Teaching assisstant

Study Record Dates

• First Submitted: July 16, 2023
• First Posted: July 27, 2023
• Study Start: August 7, 2023
• Primary Completion: September 20, 2024
• Study Completion: September 20, 2024
• Last Updated: August 12, 2025

Record last verified: 2025-08

Locations

EG (1)