Tenapanor in Synucleinopathy-Related Constipation

Recruitment & Eligibility

Inclusion Criteria

To be considered for inclusion, subjects of all sexes must be between the ages of 50 and 89 years. Patients of child-bearing potential must agree to use appropriate methods of contraception, be post-menopausal or sterile. Subjects must meet the diagnosis of PD (with active disease within Hoehn and Yahr stages 1-3) as diagnosed by a neurologist according to criteria set forth by the International Parkinson and Movement Disorder Society, of which our investigators are members and contributors.
In the 6 months prior to screening, included patients must report average weekly stool frequency of 5 or fewer spontaneous bowel movements (SBMs) with 2 or fewer complete spontaneous bowel movements (CSBMs) with sensation of complete evacuation, and must have an average weekly stool consistency of 3 or less using the Bristol Stool Form Scale (BSFS). Over-the-counter laxative use is permitted as needed at baseline and during the course of the study (includes PEG solutions, senokot, bisacodyl, and magnesium)

Exclusion Criteria

General exclusion criteria are functional diarrhea, IBS-D/M as defined by Rome IV Criteria, symptomatic structural abnormality of the GI tract, inflammatory bowel disease, hepatic dysfunction (ALT or AST ≥ 2.5x the upper limit of normal), renal impairment (serum creatinine >2mg/dl), pregnancy, lactation, and presence of significant disease that will limit participation within the 6 months before screening. Patients will also be excluded if they have dyssynergic defecation, diagnosed clinically or by anorectal manometry as failure to relax or inappropriate contraction of the puborectalis and external anal sphincter muscles as pressure increases in the rectum.
Use of prescription laxatives (ie. linaclotide, naloxegol, lubiprostone).

Study & Design

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo orally twice daily for 12 weeks
Tenapanor	Tenapanor	Tenapanor 50 mg orally twice daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Complete spontaneous bowel movements (CSBM)	6 of 12 weeks	Our primary endpoint will be CSBM response, defined as an increase of at least one CSBM per week compared to baseline for at least 6 of the 12 treatment weeks. A CSBM is defined as a bowel movement that occurs naturally and is accompanied by a feeling of complete evacuation

Secondary Outcome Measures

Name	Time	Method
Abdominal pain and bloating response	6 of 12 weeks	Decrease in severity score of at least 20% or more from baseline in 6 of 12 weeks
GIDS-PD	Week 12	GIDS-PD improvement of 20%, where score ranges 1-108, or a 20% improvement in constipation, bowel irritability, or upper GI subscores
Calprotectin	Week 12	Decrease in fecal calprotectin by 20% or greater
Lipopolysaccharide binding protein	Week 12	Decrease in serum lipopolysaccharide binding protein by 20%
Movement symptoms	Week 12	MDS-UPDRS total improvement by 20% compared to baseline
CSBM continuous	Week 12	CSBM treated as a continuous variable. We expect an increase of CSBMs in the treatment group compared to the placebo group.

Recruitment & Eligibility