Using pyridostigmine to treat constipation in Parkinson's disease

Pyridostigmine for the Treatment of Constipation in Parkinson Disease

This study is testing if pyridostigmine can help people with Parkinson's disease who struggle with chronic constipation feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Vermont Medical Center (Academic / other)
• Locations: 1 site (Burlington, Vermont)
• Trial ID: NCT05603715 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of pyridostigmine, a medication typically used for myasthenia gravis, in treating chronic constipation among patients with Parkinson's disease. The study is designed as a 13-15 week open-label, dose escalation trial where participants will receive pyridostigmine at doses ranging from 60 to 180 mg taken three times a day. The trial aims to address the significant unmet need for effective treatments for constipation, a common and debilitating symptom in this patient population. By evaluating the outcomes, the study hopes to provide insights into a potential new therapeutic option for managing constipation in Parkinson's disease.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older who have been diagnosed with Parkinson's disease and experience chronic constipation.

Not a fit: Patients who do not have Parkinson's disease or those with constipation due to other underlying conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients with Parkinson's disease suffering from constipation.

How similar studies have performed: While there is limited research specifically on pyridostigmine for constipation in Parkinson's disease, the approach of using existing medications for new indications has shown promise in other studies.

Eligibility 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

Where this trial is running

Burlington, Vermont

• University of Vermont Medical Center — Burlington, Vermont, United States (Recruiting)

Study contacts

• Principal investigator: Lisa M Deuel, MD — University of Vermont
• Study coordinator: Kaysi Herrera Pujols

Conditions Parkinson Disease; Constipation