Comparison of Benzhexol and Procyclidine for Tremor in Tremor-Predominant Parkinson's Disease

NCT07810296 | Recruiting

• 1 other identifier: 751/RC/KEMU
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare benzhexol and procyclidine for improving tremor in adults with tremor-predominant Parkinson's disease who are taking levodopa. Researchers will compare the two medicines to determine whether benzhexol provides similar improvement in tremor to procyclidine and to assess their side effects. Participants will be randomly assigned to receive either benzhexol or procyclidine in addition to their usual levodopa treatment. Motor symptoms and side effects will be assessed before treatment and at 2 weeks, 3 months, and 6 months.

Conditions

Parkinson Disease (PD)

Keywords

Tremor; Tremor-Predominant Parkinson Disease; Benzhexol; Procyclidine; Anticholinergic

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Total Tremor Subset Score of the MDS-UPDRS Part III at 2 Weeks

  The total tremor subset score is the sum of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III tremor items: postural tremor of the right hand, postural tremor of the left hand, kinetic tremor of right hand, kinetic tremor of left hand, rest tremor amplitude of the right upper extremity, rest tremor amplitude of the left upper extremity, rest tremor amplitude of the right lower extremity, rest tremor amplitude of the left lower extremity, rest tremor amplitude of the lip/jaw, and constancy of rest tremor. The minimum score is 0 and maximum score is 40 for tremor subset scores with a lower score indicating better function. Change from baseline will be calculated as the baseline total score minus the total score at 2 weeks, with a greater positive change representing greater improvement in tremor.

  From Baseline to Week 2

Secondary Outcomes (1)

• Total Number of Side Effects

  From Baseline to 6 months

Study Arms (2)

Benzhexol

EXPERIMENTAL

Participants will receive benzhexol in addition to levodopa/carbidopa therapy. Benzhexol will be started at 2 mg on day 1, increased to 2 mg twice daily on day 4 and to 2 mg three times daily on day 7. The dose will subsequently be adjusted according to resolution of tremor or development of side effects. If tremor resolves, benzhexol will be continued at the effective dose; if intolerable side effects develop, the dose will be reduced and subsequently stopped if side effects persist. Participants will be followed for 6 months with assessments at baseline, 2 weeks, 3 months, and 6 months.

Drug: Benzhexol

Procyclidine

ACTIVE COMPARATOR

Participants will receive procyclidine in addition to levodopa/carbidopa therapy. Procyclidine will be started at 2.5 mg three times daily on day 1, increased to 5 mg in the morning plus 2.5 mg in the afternoon and evening on day 3, then to 5 mg in the morning and afternoon with 2.5 mg in the evening on day 5, and finally up to 5 mg three times daily on day 7. The dose will subsequently be adjusted according to resolution of tremor or development of side effects. If tremor resolves, procyclidine will be continued at the effective dose; if intolerable side effects develop, the dose will be reduced and subsequently stopped if side effects persist. Participants will be followed for 6 months with assessments at baseline, 2 weeks, 3 months, and 6 months.

Drug: Procyclidine

Interventions

Benzhexol DRUG

Benzhexol will be administered orally. Treatment will start at 2 mg on day 1, increase to 2 mg twice daily on day 4, and increase to 2 mg three times daily on day 7. The dose will subsequently be adjusted according to tremor response and tolerability. Treatment will continue for up to 6 months unless stopped because of persistent intolerable side effects.

Benzhexol

Procyclidine DRUG

Procyclidine will be administered orally. Treatment will start at 2.5 mg three times daily on day 1, increase to 5 mg in the morning plus 2.5 mg in the afternoon and evening on day 3, then to 5 mg in the morning and afternoon with 2.5 mg in the evening on day 5, and finally up to 5 mg three times daily on day 7. The dose will subsequently be adjusted according to tremor response and tolerability. Treatment will continue for up to 6 months unless stopped because of persistent intolerable side effects.

Procyclidine

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed Parkinson's disease according to the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease, with predominant tremor at presentation.
• Hoehn and Yahr stage 1, 2, or 3.
• Any gender.
• Age 40 to 70 years.
• Receiving levodopa/carbidopa monotherapy for Parkinson's disease, with resting tremor present.

You may not qualify if:

• Cognitive or behavioral abnormalities.
• Lower urinary tract symptoms.
• Benign prostatic hyperplasia.
• Angle-closure glaucoma.
• Cardiac disease.

Sponsors & Collaborators

• safia bano: lead

Study Sites (1)

Mayo Hospital Lahore

Lahore, Punjab Province, 54000, Pakistan

RECRUITING

Related Publications (8)

• Habib, Md. Ahsan & Alamgir, ASM & Dey, Subash Kanti & Alam, Afroja & Asafuddoula, Ahmed & Rizvi, Abu. (2016). Effect of Trihexiphenidyl and Procyclidine for the management of resting tremor. Bangladesh Medical Journal. 44. 72-75. 10.3329/bmj.v44i2.27241.

  BACKGROUND

• Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340.

  PMID: 19025984 BACKGROUND

• Sahoo LK, Holla VV, Batra D, Prasad S, Bhattacharya A, Kamble N, Yadav R, Pal PK. Comparison of effectiveness of trihexyphenidyl and levodopa on motor symptoms in Parkinson's disease. J Neural Transm (Vienna). 2020 Dec;127(12):1599-1606. doi: 10.1007/s00702-020-02257-0. Epub 2020 Oct 9.

  PMID: 33037478 BACKGROUND

• Barrett MJ, Sargent L, Nawaz H, Weintraub D, Price ET, Willis AW. Antimuscarinic Anticholinergic Medications in Parkinson Disease: To Prescribe or Deprescribe? Mov Disord Clin Pract. 2021 Oct 8;8(8):1181-1188. doi: 10.1002/mdc3.13347. eCollection 2021 Nov.

  PMID: 34765683 BACKGROUND

• Lees A, Tolosa E, Stocchi F, Ferreira JJ, Rascol O, Antonini A, Poewe W. Optimizing levodopa therapy, when and how? Perspectives on the importance of delivery and the potential for an early combination approach. Expert Rev Neurother. 2023 Jan;23(1):15-24. doi: 10.1080/14737175.2023.2176220. Epub 2023 Feb 10.

  PMID: 36729395 BACKGROUND

• Vazquez-Velez GE, Zoghbi HY. Parkinson's Disease Genetics and Pathophysiology. Annu Rev Neurosci. 2021 Jul 8;44:87-108. doi: 10.1146/annurev-neuro-100720-034518.

  PMID: 34236893 BACKGROUND

• Peng S, Liu P, Wang X, Li K. Global, regional and national burden of Parkinson's disease in people over 55 years of age: a systematic analysis of the global burden of disease study, 1991-2021. BMC Neurol. 2025 Apr 23;25(1):178. doi: 10.1186/s12883-025-04191-8.

  PMID: 40269818 BACKGROUND

• Ou Z, Pan J, Tang S, Duan D, Yu D, Nong H, Wang Z. Global Trends in the Incidence, Prevalence, and Years Lived With Disability of Parkinson's Disease in 204 Countries/Territories From 1990 to 2019. Front Public Health. 2021 Dec 7;9:776847. doi: 10.3389/fpubh.2021.776847. eCollection 2021.

  PMID: 34950630 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Tremor

Interventions

Trihexyphenidyl; Procyclidine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrrolidines

Central Study Contacts

Saad A Malik, MBBS

CONTACT

+92-3005107713; saadazhar@live.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor Neurology

Model Details: Participants will be randomly assigned to one of two parallel treatment groups. Group A will receive benzhexol and Group B will receive procyclidine in addition to levodopa therapy. Participants will be followed for 6 months, with assessments at baseline, 2 weeks, 3 months, and 6 months.

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 9, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 14, 2026

Record last verified: 2026-09

Locations

PA (1)