Double‐Blind, Randomized, Placebo‐Controlled Trial of DA‐9701 in Parkinson's Disease: PASS‐GI Study

Abstract

A BS TRACT: Objectives: This study aimed to assess the efficacy of DA-9701 on gastrointestinal symptomrelated quality of life in patients with Parkinson's disease on stable dopaminergic medications. Methods: This multicenter, double-blind, placebo-controlled, phase 4 trial included a total of 144 patients with Parkinson's disease with gastrointestinal dysfunctions based on predefined criteria. Participants were randomized to take either DA-9701 or placebo for 4 weeks, and then both groups were administered DA-9701 for an additional 8 weeks while antiparkinsonian medications were unchanged. The primary outcome measure was gastrointestinal symptoms and related quality-of-life changes assessed on the Korean Nepean dyspepsia index after 4 and 12 weeks of therapy. We also evaluated the impact of DA-9701 therapy on parkinsonian motor symptoms at each time point. Results: The gastrointestinal symptom-related quality-oflife score significantly improved in the DA-9701-treated group compared with the placebo-treated group after 4weeks (adjusted P = 0.012 by linear mixed effect model analysis). The overall gastrointestinal symptom and dyspepsia sum scores improved at 12 weeks after intervention in the DA-9701-first treated group (adjusted P = 0.002 and 0.014, respectively) and also in the placebo-first treated group (adjusted P = 0.019 and 0.039) compared with the baseline. Parkinsonian motor severity was not significantly affected by DA-9701 treatment in both groups at 4 and 12 weeks after intervention. There were no drugrelated serious adverse events throughout the trial. Conclusions: DA-9701 therapy improved gastrointestinal symptom-related quality of life, and 12 weeks of daily administration can relieve the overall severity of gastrointestinal symptoms in patients with Parkinson's disease without affecting motor symptoms.

Dietary intake and plasma levels of polyunsaturated fatty acids in early-stage Parkinson’s disease

“…Demographic factors, co-morbidity, and other lipid levels were previously described 24 and did not differ between patients with PD and controls. In contrast, the Wexner constipation score and Korean version of the Non-Motor Symptom Scale (K-NMSS) scores were significantly higher in patients with PD than in controls (Table 1 ).…”

“…Patients were diagnosed with PD according to the United Kingdom Parkinson’s Disease Society Brain Bank Clinical Diagnosis Criteria 45 . The inclusion criteria were as follows: patients not receiving antibiotics, immune-related drugs, and vaccines (for 3 months), lipid-lowering drugs (for 1 month), and vitamin supplements, n-3 fatty acids, prebiotics, and probiotics (for 2 weeks) 24 . The exclusion criteria were as follows: patients with secondary parkinsonism, other significant central nervous system diseases, malignancy within the last 3 years, and significant gastrointestinal disorders 24 .…”

“…The inclusion criteria were as follows: patients not receiving antibiotics, immune-related drugs, and vaccines (for 3 months), lipid-lowering drugs (for 1 month), and vitamin supplements, n-3 fatty acids, prebiotics, and probiotics (for 2 weeks) 24 . The exclusion criteria were as follows: patients with secondary parkinsonism, other significant central nervous system diseases, malignancy within the last 3 years, and significant gastrointestinal disorders 24 . Healthy control subjects were recruited from volunteers via posters on notice boards in the hospital and the patients’ spouses.…”

Gastrointestinal Dysfunction in Parkinson’s Disease: Neuro-Gastroenterology Perspectives on a Multifaceted Problem

“…Treatment with the plant-based prokinetic DA-9701 for 12 weeks improved dyspepsia severity scores in a double-blind randomized placebo-controlled trial (DB-RPCT) (n = 144), and no serious adverse events were reported. 41 H. pylori infection, which has been causatively linked to dyspepsia, peptic ulcer disease, and gastric carcinoma, is a major public health issue worldwide, especially in Asia, Africa, and Latin America. 42 Guidelines recommend that patients with dyspepsia (with or without red flag symptoms) should undergo H. pylori testing, which is easily performed using a non-invasive 13 C urea breath test or a stool antigen test.…”

“…However, specific evidence in PD is relatively lacking (Table 1). 4,15,41,[61][62][63][64][65][66][67] Domperidone is a peripheral dopamine D2 receptor antagonist that is relatively impermeable to the bloodbrain barrier, and it is a commonly used prokinetic agent. Domperidone improved GE time, gastroparesis symptoms and levodopa bioavailability in two small studies in PD.…”