28. THRIVE-1: A Multi-Center, Cross-Sectional, Observational Study To Assess the Prevalence of Choline Deficiency in Patients Dependent on Parenteral Support

Background: Choline is a quaternary amine that is an essential dietary nutrient in humans. Choline is essential for patients with intestinal failure (IF) who are dependent on Parenteral Support (PS), given that deficiency can lead to hepatic injury, neuropsychological impairment, muscle damage, and thrombotic abnormalities. Current PS formulations lack choline, affecting an estimated 40,000 long-term PS patients who are or may become deficient. Currently, there are no approved intravenous (IV) choline products for PS patients globally.

Purpose: The purpose of this study was to assess the prevalence of choline deficiency in patients dependent on PS (defined as at least 4 days/week on PS for 10 to 24 weeks [capped at 25%] and 24 weeks or longer) and to identify those who might benefit from innovative treatments, including IV Choline Chloride.

Methods: THRIVE-1 was a multi-center, cross-sectional observational study to assess the prevalence of choline deficiency and liver injury in adolescents (≥ 12 years of age) and adult patients (≥ 18 years of age) with IF who are dependent on PS. Data collection occurred during a single clinic visit.

Results: Of 78 enrolled patients, 55% were male, 92% White, and 96% Not Hispanic or Latino. Mean age was 52 years (SD: 16.6), height was 167.59 cm (SD: 10.2), weight was 64.73 kg (SD: 13.5), and BMI was 22.95 kg/m² (SD: 3.8). Patients had received PS for a mean duration of ~9 years and a PS frequency of 6.6 days/week (SD: 0.95). Most patients received mixed (40%, 31/78) or plant-based lipids (49%, 38/78). Patients had at least one of the following underlying conditions based on ESPEN Pathophysiological IF Classification: 59% (46/78) Short Bowel Syndrome, 46% (36/78) Mucosal Diseases, 33% (26/78) Chronic Intestinal Dysmotility Disorders, 8% (6/78) Mechanical Obstruction, and 6% (5/78) Intestinal Fistulae. Approximately 78% (61/78) were choline deficient (defined as plasma free choline concentration < 9.5 nmol/mL), with a mean plasma free choline concentration of 7.5 nmol/mL (SD: 3.9). Approximately 63% (38/60) of choline deficient patients had liver injury (defined as elevated liver tests [> 1.5*ULN; ALP, AST, ALT, GGT, direct bilirubin, total bilirubin] or steatosis [MRI-PDFF ≥ 8%]).

Discussion: The THRIVE-1 study highlights a significant prevalence of choline deficiency (~78%) among PS-dependent patients. A strong association was found between choline deficiency and liver injury, with 63% of deficient patients showing signs of liver damage. The study population was predominantly White and non-Hispanic, yet the diversity of underlying conditions suggests that choline deficiency is a widespread issue across various etiologies of intestinal failure.

Conclusions: The high prevalence of choline deficiency among patients with IF dependent on PS underscores the urgent need for choline supplementation. This population has a significant unmet need for IV choline that should be addressed. The observed heterogeneity in liver injury also warrants further investigation. Choline Chloride for Injection, a phospholipid substrate replacement therapy, is being developed as a source of choline to potentially enhance health outcomes for long-term PS-dependent patients.