Design and rationale for a pilot trial of D-alanine supplementation to reduce the triglyceride to high-density lipoprotein cholesterol ratio in patients with chronic kidney disease.

The authors previously demonstrated a significant association between a high TG/HDL-C ratio and CKD progression and cardiovascular disease in CKD patients.

• This prior finding forms the primary rationale for investigating the TG/HDL-C ratio as a therapeutic target in CKD patients.
• The association encompassed both CKD progression and cardiovascular disease outcomes.
• Dyslipidemia's association with CKD is described as remaining unclear despite CKD's linkage to lifestyle-related diseases.

D-alanine has been reported to regulate circadian rhythms, participate in gluconeogenesis, and exhibit renoprotective effects.

• These properties of D-alanine provide the mechanistic rationale for its potential benefit on the TG/HDL-C ratio in CKD patients.
• D-alanine is described as a recent focus of reports linking it to metabolic and renal functions.
• The renoprotective effects of D-alanine are cited as a basis for its investigation in a CKD population specifically.

The trial is designed as an open-label, multicenter, single-arm, exploratory study enrolling 20 CKD patients over 10 weeks.

• The 10-week study period includes a 2-week run-in period, a 4-week treatment period, and a 4-week follow-up period.
• Patients will be recruited from Nara Medical University and Nara Prefectural General Medical Center.
• The single-arm design reflects the exploratory and pilot nature of the trial.

The primary endpoint of the trial is the change in fasting TG/HDL-C ratio between baseline and Day 28.

• Day 28 corresponds to the end of the 4-week treatment period.
• The study will summarize absolute measurements and changes using descriptive statistics, confidence intervals, and line graphs showing means ± confidence intervals.
• A two-tailed significance level of p < 0.05 will be used.

Secondary endpoints include a broad range of metabolic, renal, and cardiovascular parameters measured between baseline and Day 28.

• Secondary endpoints include changes in fasting TG, HDL-C, and LDL cholesterol.
• Liver function markers (AST and ALT), glycated hemoglobin A1c, systolic and diastolic blood pressure are included.
• Renal-specific endpoints include proteinuria and estimated glomerular filtration rate.
• Body weight is also included as a secondary endpoint.

The protocol received ethics approval and was registered in a public clinical trial registry prior to enrollment.

• Approval was granted by the Clinical Trial Review Board of Nara Medical University Clinical Research Review Committee (CRB5200002) on February 5, 2025.
• The protocol was registered on the Japan Registry of Clinical Trials on December 18, 2024 (jRCTs051240262).
• The trial is described as exploratory in nature, aiming to evaluate both efficacy and safety of D-alanine for treating dyslipidemia in CKD patients.