Pyridostigmine for the Treatment of Constipation in Parkinson Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 26 June 2023
• Main ID: NCT05603715
• Date of registration: 12/09/2022
• Prospective Registration: No
• Primary sponsor: University of Vermont Medical Center
• Public title: Pyridostigmine for the Treatment of Constipation in Parkinson Disease
• Scientific title: Pyridostigmine for the Treatment of Constipation in Parkinson Disease
• Date of first enrolment: August 10, 2022
• Target sample size: 16
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT05603715
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Lisa M Deuel, MD

• Name: Lisa M Deuel, MD
• Affiliation: University of Vermont

• Name: Katherine Chan

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age = 18 years

2. Be able to provide signed informed consent

3. Stated ability and willingness to comply with all study procedures

4. Able to take oral medications

5. Females of reproductive potential who are sexually active must be willing to use two
of the following highly effective methods of contraception for the duration of study
participation and for an additional 28 days after the end of study drug
administration: barrier contraception (female condom, diaphragm, cervical cap
with/without spermicide), hormonal contraception, or intrauterine device; OR one of
the previously mentioned methods AND partner must use barrier contraception (male
condom with/without spermicide)

6. Males of reproductive potential who are sexually active must be willing to use the
following highly effective methods of contraception for the duration of study
participation and for an additional 28 days after the end of study drug
administration: barrier contraception (male condom with/without spermicide) AND
partner must be postmenopausal, use hormonal contraception, have an intrauterine
device, or use barrier contraception (female condom, diaphragm, cervical cap
with/without spermicide)

7. Meet United Kingdom Parkinson's Disease Society Brain Bank Criteria:

A. Diagnosis of a parkinsonism:

- Bradykinesia, plus at least one of the following:

- Muscular rigidity

- 4-6 Hz resting tremor

- Postural stability not caused by primary visual, vestibular, cerebellar or
proprioceptive dysfunction

B. At least three supportive criteria:

- Unilateral onset of symptoms

- Rest tremor

- Progressive symptoms

- Persistent asymmetry affecting the side of onset most

- Excellent response to levodopa

- Severe levodopa-induced chorea

- Levodopa response for five years or more

- Clinical course of 10 years or more

8. Fulfill the ROME IV Criteria for Functional Constipation, with a specific requirement
that the patient must have three or fewer defecations per week (criterion Ai):

- Must include two or more of the following:

i. Three or fewer defecations per week ii. Straining during > 25% of defecations
iii. Lumpy or hard stools in > 25% of defecations iv. Sensation of incomplete
evacuation for > 25% of defecations v. Sensation of anorectal
obstruction/blockage for > 25% of defecations vi. Manual maneuvers to facilitate
> 25% of defecations

- Loose stools are rarely present without the use of laxatives

- Insufficient criteria for irritable bowel syndrome

- Criteria 1-3 must be fulfilled for at least three months with onset of symptoms
at least six months prior to diagnosis

Exclusion Criteria:

1. Diagnosis of atypical parkinsonism

2. Diagnosis of drug-induced parkinsonism

3. Diagnosis of vascular parkinsonism

4. Known allergy to pyridostigmine bromide or other study drug components

5. Current or recent (within 90 days of enrollment) use of pyridostigmine for any reason

6. History of any bowel surgery

7. History of bladder or bowel obstruction

8. Severe asthma or chronic obstructive pulmonary disease

9. Meet exclusion criteria noted in the UK Parkinson's Disease Society Brain Bank
Criteria, at the PI's discretion:

A.Exclusion of any of the following:

- Repeated strokes with stepwise progression of parkinsonian features

- Repeated head injury

- Definite encephalitis

- Oculogyric crises

- Neuroleptic treatment at onset of symptoms

- Greater than one affected relative

- Sustained remission

- Strictly unilateral features after 3 years

- Supranuclear gaze palsy

- Cerebellar signs

- Early severe autonomic involvement

- Early severe dementia

- Babinski sign

- Cerebral tumor or communicating hydrocephalus

- Negative response to large doses of levodopa

- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure

10. Significant abnormalities on laboratory analysis (complete blood count, comprehensive
metabolic panel, thyroid stimulating hormone) conducted at the screening visit or
within the three months prior if available for review

11. Significant abnormalities on screening electrocardiogram conducted at the screening
visit or within the three months prior if available for review

12. Positive pregnancy test (if female of child-bearing age)

13. Antibiotic use within two weeks prior to enrollment



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Constipation

Parkinson Disease

Intervention(s)

Drug: Pyridostigmine Bromide

Primary Outcome(s)

Change in number of spontaneous bowel movements per week after the study intervention [Time Frame: 13-15 Weeks]

Secondary Outcome(s)

Changes from Baseline to the End of Study Visit in the International Parkinson and Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) [Time Frame: 9-11 Weeks]

Changes from Baseline to the End of Study Visit in Beck Depression Inventory-II (BDI-II) [Time Frame: 9-11 Weeks]

Changes from Baseline to the End of Study Visit in the Cleveland Clinic Constipation Scoring System (CCCSS) [Time Frame: 9-11 Weeks]

Changes from Baseline to the End of Study Visit in the Gastrointestinal Dysfunction Scale in Parkinson's Disease (GIDS-PD) [Time Frame: 9-11 Weeks]

Number of adverse events and serious adverse events that occur during the trial [Time Frame: 13-15 Weeks]

Changes from Baseline to the End of Study Visit in the MDS-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-IV [Time Frame: 9-11 Weeks]

Changes from Baseline to the End of Study Visit in the Parkinson's Disease Questionnaire (PDQ-39). [Time Frame: 9-11 Weeks]

Secondary ID(s)

STUDY00001877

Source(s) of Monetary Support

Please refer to primary and secondary sponsors