Role of Zonisamide in Advanced Parkinson's Disease (PD) in Egyptian Population: Pilot Study

Zonisamide (ZNS) (1,2-Benzisoxazole-3-methanesulfonamide) is an anti-epileptic drug. In three double blinded placebo controlled studies, ZNS- as an adjunctive treatment- showed beneficial effects on motor symptoms of PD with a low incidence of adverse events. As a result 25 mg daily of ZNS was approved in 2009 in Japan as an adjunctive treatment in PD patients whose condition responded insufficiently to Levodopa treatment.

Most observations of a beneficial effect of ZNS have been in Japanese people, and the antiparkinsonian mechanism of action is unclear. So, ZNS is a promising but still investigational drug to treat PD and more studies are warranted.

this study will investigate the efficacy and tolerability of Zonisamide as an adjunctive treatment in Egyptian patients with advanced PD, including motor fluctuations, levodopa induced dyskinesia and existing nonmotor symptoms. Additionally it investigates its effects on quality of life of PD patients.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Zonisamide Capsules

Detailed Description

Type of Study: Randomized double blinded Placebo controlled study.

• Study Setting: Movement disorders clinic of neurology department, Ain Shams University Hospitals.
• Study Period : 2 years.
• Study Population: Patients with advanced PD and insufficient response to dopaminergic drugs .

Inclusion Criteria:

• Age older than 18 years of both male and female genders.
• Individuals diagnosed with PD based on the presence of 2 of 3 cardinal features & United Kingdom bank criteria for idiopathic Parkinson's disease.
• Patients with manifestations of advanced PD defined according to the consensus on the definition of advanced PD.
• Inadequate response to dopaminergic medications due to limitations related to side effects, or levodopa related long-term problems as wearing-off phenomena, "on"-"off" fluctuation, levodopa induced dyskinesia and freezing phenomena, no-"on" and delayed-"on,".

Exclusion Criteria:

1. Patients with atypical or secondary parkinsonian syndromes excluding PD.
2. Patients who could not perform the tests.
3. Women who were or might be pregnant, who did not practice effective contraception and were of childbearing potential, or who were breastfeeding.

Ethical Considerations:

All of the patients will be informed of the objectives, procedures and possible benefits and risks of the study and will provide written voluntary consent.

The study will conform to the standards of the Ethical Review Committee, Ain Shams University.

Study Procedures:

- Patients diagnosed with PD will be evaluated for inclusion and exclusion criteria. Eligible patients will be randomly assigned to one of three groups: placebo group , ZNS group 25 mg and ZNS group 50 mg (30 patients each).In ZNS 50 mg group, ZNS will be started with a dose of 25 mg daily for one week then increased to 50 mg once daily to minimize side effects. The dosage and regimen of ongoing antiparkinsonian drugs and other drugs that may affect PD symptoms will remain unchanged one month before and through the treatment period.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ali S Shalash, PhD; Phone Number: 00201111124815; Email: ali_neuro@yahoo.com
• Study Contact Backup: Name: Mohamed Essam, MD; Email: dmohamedesam@gmail.com

Study Locations

• Egypt
  • Cairo, Egypt, 11591
    • Ain Shams Univeristy
  • Abbasia
    • Cairo, Abbasia, Egypt, 11575
      • Department of Neurology, Ain Shams University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1 -Age older than 18 years of both male and female genders. 2-Individuals diagnosed with PD based on the presence of 2 of 3 cardinal features & UK bank criteria for idiopathic Parkinson's disease. 3-Patients with motor complications of PD (Hoehn and Yahr stage 2-3)(on therapy) and at least 2 hours off time.

Exclusion Criteria:

1 -Patients with atypical or secondary Parkinsonism syndromes excluding PD. 2-Patients who could not perform the tests. 3-Women who were or might be pregnant, who did not practice effective contraception and were of childbearing potential, or who were breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patients 25 ZNS; 30 patients receive oral 25 mg ZNS daily	Drug: Zonisamide Capsules; anti-epileptic drug that recently used as add on therapy of wearing off and fluctuation complications of dopaminergic drugs in PD patients; Other Names: Convagran
Active Comparator: Patients 50 ZNS; 30 patients receive oral 50 mg ZNS daily	Drug: Zonisamide Capsules; anti-epileptic drug that recently used as add on therapy of wearing off and fluctuation complications of dopaminergic drugs in PD patients; Other Names: Convagran
Placebo Comparator: Patients Placebo; 30 patients receive placebo	Drug: Zonisamide Capsules; anti-epileptic drug that recently used as add on therapy of wearing off and fluctuation complications of dopaminergic drugs in PD patients; Other Names: Convagran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Off motor daily time	assessing change of Off and on time using Movement Disorders Society- Unified Parkinson's Disease Rating Scale (MDS UPDRS)	at 1 and 3 months
levodopa related Dyskinesia	Dyskinesia will also be evaluated with Movement Disorders Society- Unified Dyskinesia Rating Scale (MDS-UDysRS)	at 1 and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life (daily life activities)	parkinson disease questionnaire-39	at 3 months
cognitive outcome	using Montreal cognitive assessment	at 3 months
The non-motor symptoms scales	using The non-motor symptoms scales (NMSS)	at 1 and 3 months

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: November 24, 2019
• First Submitted That Met QC Criteria: November 28, 2019
• First Posted (Actual): December 2, 2019

Study Record Updates

• Last Update Posted (Actual): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson's disease, zonisamide, motor, fluctuation
• 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; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Zonisamide
• Other Study ID Numbers: MD282/2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No