Pyridostigmine for the Treatment of Constipation in Parkinson Disease
Constipation is a common and debilitating non-motor symptom of Parkinson disease (PD) that often precedes the onset of classic motor symptoms by decades. There is no standardized algorithm for managing constipation in this patient population, nor are there dedicated treatments. Studies suggest that constipation can affect quality of life to a significant degree, in many cases just as much as motor symptoms. There is an unmet need for effective treatment options for constipation in this patient population. The goal of this study is to determine the efficacy and safety of pyridostigmine as a treatment for chronic constipation in patients with PD.
• Age ≥ 18 years
• Be able to provide signed informed consent
• Stated ability and willingness to comply with all study procedures
• Able to take oral medications
• 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)
• 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)
• 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
• 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