Cilostazol in Parkinson's Disease

NCT06612593 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: RHDIRB2020110301 REC # 282
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Parkinson's disease is the second most common neurodegenerative diseases. The conventional treatment for PD has included dopaminergic treatment as Levodopa\\carbidopa or dopamine agonists, anti-cholinergics, MAOI, catechol-o-methyl transferase (COMT) inhibitors, and amantadine. Although these options have been found to be effective, they could only improve the disease symptoms, but do not modify the disease progression. Hence, researchers have focused on developing disease-modifying agents to stop or slow the progression acting as neuroprotective agents. Since the inflammation and oxidative stress play an important role in the pathophysiologic progression of PD, recent studies have investigated the mitigation of the disease pathology through anti-inflammatory and anti-oxidant agents. Cilostazol has been found to have anti-inflammatory, antioxidant, and neuroprotective effect, and has been evaluated through two animal studies to prove that it possess these effects through dampening NF-κB, and its downstream effectors including TNF-α and IL-1β, reversing the activation of glycogen synthase kinase-3 β (GSK-3β), a pivotal effector in neuronal apoptosis, contributing in preserving dopaminergic neuron integrity clarifying the enhance motor activity, activating nuclear factor erythroid-related factor 2/ heme oxygenase 1 (Nrf2/HO-1), suppressing High mobility group box 1 protein/Toll-like receptor 4 (HMGB1/TLR4) axis, and upregulatig Phosphoinositide 3-kinases/ Protein kinase B (PI3K/Akt) besides mammalian target of rapamycin (mTOR) inhibition. Hence, Cilostazol might be a potential candidate to improve the clinical outcome in PD patients.

Conditions

Parkinson's Disease

Keywords

PD, Parkinson's Disease, Cilostazol, Neuroinflammation, Oxidative Stress, Anti-inflammatory, Anti-oxidant, Neuroprotective, MDS-UPDRS

Outcome Measures

Primary Outcomes (1)

• Assessment of the severity of Parkinson's disease symptoms using the Movement Disorder Society-unified Parkinson's disease rating scale (MDS-UPDRS)Assessment

  MDS-UPDRS will be performed at baseline, after 12weeks and after 24 weeks. MDS-UPDRS, the revised form of UPDRS, is the most common tool used to measure progression in PD patients. It consists of 4-subscale structure: Part I, Non-Motor Aspects of Experiences of Daily Living (13 items); Part II, Motor Aspects of Experiences of Daily Living (13 items); Part III, Motor Examination (33 items); and Part IV, Motor Complications (6 items). The scores in each item vary from 0 (normal) to 4(severe).

  6 months

Secondary Outcomes (4)

• Serum Level of BDNF Assessment:

  6 months

• Safety Assessment

  6 months

• Assessment of the degree of cognitive impairment with The Montreal Cognitive Assessment (MoCA)

  6 months

• Assessment of Quality of life (QoL) USING the PDQ-39 questionnaire

  6 months

Study Arms (2)

Cilostazol Group

EXPERIMENTAL

25 participants will receive the standard treatment and cilostazol at a dose of 50 mg twice daily for a month, then the dose will be increased to 100 mg twice daily for 5 months.

Drug: Cilostazol; Drug: Standard treatment

Control Group

ACTIVE COMPARATOR

25 participants will receive the standard treatment and the placebo twice daily for 6 months.

Drug: Placebo; Drug: Standard treatment

Interventions

Cilostazol DRUG

2 tablets of 50 mg cilostazol will be received for 4 weeks, then the does will be 2 tablets of 100 mg cilostazol twice daily for 20 weeks

Cilostazol Group

Placebo DRUG

The patient will receive 2 tablets twice daily

Control Group

Standard treatment DRUG

It includes Levodopa with a dose of 375 to 1000mg daily and Dopamine agonists with a dose of 1.5 to 5 mg daily.

Cilostazol Group; Control Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients.
• Both males and females will be included
• Diagnosed Parkinson's disease according to the MDS criteria 2015
• At least 5 years of disease duration
• On stable Levodopa\\carbidopa regimen for the past 6 months.
• Clinically diagnosed with dyskinesia

You may not qualify if:

• Secondary causes of Parkinsonism
• Atypical parkinsonian syndromes
• Active malignancy
• Known intolerance or hypersensitivity to cilostazol
• Participation in other interventional trials
• Patients with hepatic (AST and ALT more than 3 times the upper normal limit) or renal impairment (eGFR less than 60 ml\\min).
• Patients receiving warfarin, other anti-coagulants or anti-platelet therapy.
• Patients with Congestive heart failure.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ain Shams University Hospital

Cairo, Egypt

Location

Related Publications (10)

• Abdallah MS, Ramadan AN, Omara-Reda H, Mansour NO, Elsokary MA, Elsawah HK, Zaki SA, Abo Mansour HE, Mosalam EM. Double-blind, randomized, placebo-controlled pilot study of the phosphodiesterase-3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder. CNS Neurosci Ther. 2021 Dec;27(12):1540-1548. doi: 10.1111/cns.13731. Epub 2021 Sep 21.

  PMID: 34545997 BACKGROUND

• Arai H, Takahashi T. A combination therapy of donepezil and cilostazol for patients with moderate Alzheimer disease: pilot follow-up study. Am J Geriatr Psychiatry. 2009 Apr;17(4):353-4. doi: 10.1097/JGP.0b013e31819431ea. No abstract available.

  PMID: 19307864 BACKGROUND

• Holden SK, Finseth T, Sillau SH, Berman BD. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort. Mov Disord Clin Pract. 2018 Jan-Feb;5(1):47-53. doi: 10.1002/mdc3.12553. Epub 2017 Sep 22.

  PMID: 29662921 BACKGROUND

• Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1993 Jan 21;328(3):176-83. doi: 10.1056/NEJM199301213280305.

  PMID: 8417384 BACKGROUND

• Hedya SA, Safar MM, Bahgat AK. Cilostazol Mediated Nurr1 and Autophagy Enhancement: Neuroprotective Activity in Rat Rotenone PD Model. Mol Neurobiol. 2018 Sep;55(9):7579-7587. doi: 10.1007/s12035-018-0923-1. Epub 2018 Feb 10.

  PMID: 29429051 BACKGROUND

• Howells DW, Porritt MJ, Wong JY, Batchelor PE, Kalnins R, Hughes AJ, Donnan GA. Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra. Exp Neurol. 2000 Nov;166(1):127-35. doi: 10.1006/exnr.2000.7483.

  PMID: 11031089 BACKGROUND

• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

  PMID: 15817019 BACKGROUND

• Rahman TT, El Gaafary MM. Montreal Cognitive Assessment Arabic version: reliability and validity prevalence of mild cognitive impairment among elderly attending geriatric clubs in Cairo. Geriatr Gerontol Int. 2009 Mar;9(1):54-61. doi: 10.1111/j.1447-0594.2008.00509.x.

  PMID: 19260980 BACKGROUND

• Safiri S, Noori M, Nejadghaderi SA, Mousavi SE, Sullman MJM, Araj-Khodaei M, Singh K, Kolahi AA, Gharagozli K. The burden of Parkinson's disease in the Middle East and North Africa region, 1990-2019: results from the global burden of disease study 2019. BMC Public Health. 2023 Jan 16;23(1):107. doi: 10.1186/s12889-023-15018-x.

  PMID: 36642724 BACKGROUND

• Sakamoto T, Ohashi W, Tomita K, Hattori K, Matsuda N, Hattori Y. Anti-inflammatory properties of cilostazol: Its interruption of DNA binding activity of NF-kappaB from the Toll-like receptor signaling pathways. Int Immunopharmacol. 2018 Sep;62:120-131. doi: 10.1016/j.intimp.2018.06.021. Epub 2018 Jul 10.

  PMID: 30005227 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Neuroinflammatory Diseases

Interventions

Cilostazol

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Alia Hassan Mansour, Ph.D., MD.

CONTACT

+201001103780; Alia.hassan@med.asu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Pharmacist

Model Details: Prospective Randomized Single-blinded Controlled trial

Study Record Dates

• First Submitted: September 22, 2024
• First Posted: September 25, 2024
• Study Start: October 1, 2024
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: September 25, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)