Dulaglutide for peritoneal dialysis in diabetic kidney disease

ISRCTN	ISRCTN13300160
DOI	https://doi.org/10.1186/ISRCTN13300160
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	Nil known
Sponsor	Chang Gung Memorial Hospital
Funders	Kaohsiung Chang Gung Memorial Hospital, National Science and Technology Council

Submission date: 19/10/2022
Registration date: 26/10/2022
Last edited: 24/10/2022

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Taiwan has the highest rate of end-stage kidney disease or kidney failure in the world. Co-existing disease, inadequate dialysis and uremic solutes accumulate are the serious risk factors for death in patients with end-stage kidney disease. Renal replacement therapy is a therapy for patients with kidney failure that replaces kidney function. It includes hemodialysis, peritoneal dialysis, and kidney transplant. Unlike haemodialysis, an advantage of peritoneal dialysis is that it can be done at home/work without assistance, and it is better than haemodialysis to patients on maintenance dialysis. However, inadequate dialysis is the common fate in diabetic patients who receive peritoneal dialysis

Previously, we have demonstrated that gut hormones-based treatment [i.e., dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide 1 (GLP-1) agonist] increased in GLP-1 levels, in further saved the peritoneal function from peritoneal fibrosis (scar tissue) in animal study. Currently, there remains a lack of effective method for recovering the function of peritoneum in peritoneal dialysis patients. Therefore, to confirm the effectiveness of GLP1 agonist on “early prevention” of peritoneal dialysis failure is very important. The current study will test whether dulaglutide treatment will maintain the structural and functional integrity of the peritoneal membrane in peritoneal dialysis.

Who can participate?
Diabetic PD patients aged 20 - 75 years, who started PD over 3 months previously

What does the study involve?
The patients will be randomly allocated into treatment group (dulaglutide/0.75mg adjust to 1.5mg/QW; n=30) and control group (standardized pharmacotherapy only; n=30).

What are the possible benefits and risks of participating?
Potential benefits:
1. They may get a new treatment for a disease before it is available to everyone.
2. They play a more active role in their own health care.
3. Doctors and other health professionals may provide them with medical care and more frequent health check-ups as part of their treatment.
4. The study may help reduce the indicines of ultrafiltration failure and peritoneal dialysis failure, and peritonitis rate.
Potential risks:
1. There may be minor discomfort, or side effects to experimental treatment.
2. The study may require more time and attention than standard treatment would, including visits to the study site, more urine/blood tests, more treatments, or complex dosage schedules.

Where is the study run from?
Kaohsiung Chang Gung Memorial Hospital (Taiwan)

When is the study starting and how long is it expected to run for?
January 2021 to December 2026

Who is funding the study?
Kaohsiung Chang Gung Memorial Hospital (Taiwan)
National Science and Technology Council (Taiwan)

Who is the main contact?
Dr Hon-Kan Yip, han.gung@msa.hinet.net

Contact information

Dr Hon-Kan Yip
Public

No. 123, Dapi Rd.
Niaosong Dist.
Kaohsiung
83301
Taiwan

ORCID ID	0000-0002-6305-5717
Phone	+886-7-7317123 ext. 8300
Email	han.gung@msa.hinet.net

Study information

Primary study design	Interventional
Study design	Prospective single center interventional trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	To investigate the therapeutic impact of dulaglutide on preventing peritoneal dialysis dysfunction: a randomized, open-Label, controlled clinical trial and animal model
Study objectives	Dulaglutide may preserve the kidney functional integrity in diabetic kidney disease patient with peritoneal dialysis
Ethics approval(s)	Approved 23/09/2021, Chang Gung Medical Foundation IRB (No. 199, Dunhua N. Rd., Songshan Dist., Taipei City 105406, Taiwan (R.O.C.); +886-3-3196200 ext.3705; tsengshui@cgmh.org.tw), ref: 202101696A3
Health condition(s) or problem(s) studied	Diabetes and peritoneal dialysis
Intervention	We will prospectively and consecutively enroll the diabetic peritoneal dialysis patients (n=60) to participate this clinical trial. Study subjects will be randomly allocated by sealed envelope into the treatment group (dulaglutide/0.75 mg adjust to 1.5 mg/QW; n=30) and the control group (standardized pharmacotherapy, including antihyperglycemic medicines; n=30). The dulaglutide therapy will be maintained for one year, and the patients will be followed up for one year to answer the primary and secondary endpoints.
Intervention type	Drug
Phase	Phase I
Drug / device / biological / vaccine name(s)	Dulaglutide
Primary outcome measure(s)	1. Change from Baseline in the Mean Peritoneal Fluid Glucose ratio (D4/D0) after 12 Months of Treatment with Dulaglutide. [Time Frame: baseline, 6 months and 12 months] The mean glucose concentrations will be evaluated by the Peritoneal Equilibrium Test from Baseline and after 6 and 12 months with Dulaglutide treatment. The peritoneal equilibration test (PET) characterizes the peritoneal transport of fluid, creatinine and urea using a 4.5% dextrose peritoneal fluid. The concentration of glucose in the dialysis fluid (D4) at 4 hours is divided by the glucose in the dialysis fluid at the beginning (D0), generating the D4/D0. 2. Change from Baseline in the Mean Ultrafiltration Volume after 12 Months of Treatment with Dulaglutide. [Time Frame: baseline, 6 months and 12 months] Ultrafiltration volume from Baseline and after 6 and 12 months with Dulaglutide treatment assessment by the Peritoneal Equilibrium Test. The modified peritoneal equilibration test (PET) characterizes the peritoneal transport of fluid, creatinine and urea using a 4.5% dextrose peritoneal fluid. 3. Change from Baseline in the Mean 4 Hour Peritoneal Fluid to Plasma Creatinine (D/P) after 12 Months of Treatment with Dulaglutide. [Time Frame: baseline, 6 months and 12 months] The peritoneal equilibration test (PET) characterizes the peritoneal transport of fluid, creatinine and urea using a 4.5% dextrose peritoneal fluid. The concentration of creatinine in the dialysis fluid (D) at 4 hours is divided by the plasma creatinine (P), generating the D/P creatinine. 4. Change from Baseline in the Mean 4 Hour Peritoneal Fluid to Plasma BUN (D/P) after 12 Months of Treatment with Dulaglutide. [Time Frame: baseline, 6 months and 12 months] The peritoneal equilibration test (PET) characterizes the peritoneal transport of fluid, creatinine and urea using a 4.5% dextrose peritoneal fluid. The concentration of creatinine in the dialysis fluid (D) at 4 hours is divided by the plasma BUN (P), generating the D/P BUN. 5. According to D/P creatinine, peritoneal transport status was categorized as low (L), low average (LA), high average (HA) and high (H) (L<0.5, LA 0.5–0.64, HA 0.65–0.80, H≥0.81).
Key secondary outcome measure(s)	[Time frame: baseline (pre-treatment), and 12 months (post-treatment)]. 1. Incidence rate of ultrafiltration failure measured using patient records 2. Incidence rate of peritoneal dialysis failure (i.e., peritoneal dialysis transfer to hemodialysis) 3. Incidence rate of peritonitis measured using patient records 4. Preservation of residual renal function in dialysis patients (i.e., 24-hour urinary urea and creatinine clearance and urine total protein to creatinine ratio)
Completion date	31/12/2026

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	20 Years
Upper age limit	75 Years
Sex	All
Target sample size at registration	75
Key inclusion criteria	1. CKD with a clinical cause of diabetes mellitus 2. Age is ≥ 20 and≤ 75 years 3. The subject had been receiving peritoneal dialysis for more than 3 months. 4. The subject treat with or without OHAs or insulin treatment 5. The subject doesn’t treated with GLP-1 analogue 6. The subject is able and willing to return for required follow-up visits and examinations.
Key exclusion criteria	1. Female participants who are pregnant or breastfeeding 2. Participants who have any of the following medical conditions: 2.1. Chronic inflammatory or autoimmune diseases 2.2. Viral Hepatitis B or C liver infection, liver cirrhosis, or significant liver disease 2.3. CKD from causes other than diabetes 2.4. Cancer (malignancy) 2.5. Febrile illnesses 2.6. Age is < 20 or >75 years 2.7. The subject has a life expectancy of less than one years. 2.8. The subject has allergic reaction to any GLP-1 analogues. 2.9. HIV infection- the virus that causes AIDS 2.10. The subject is deemed by study physicians to be unsuitable for enrollment. 2.11. The subject is currently enrolled in another investigational study or registry that would directly/indirectly interfere with the current study. 2.12. The subject is unable or unwilling to return for required follow-up and examination.
Date of first enrolment	01/01/2022
Date of final enrolment	31/12/2025

Locations

Countries of recruitment

Taiwan

Study participating centre

Kaohsiung Chang Gung Memorial Hospital

No. 123, Dapi Rd.
Niaosong Dist.
Kaohsiung
83301
Taiwan

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data-sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

24/10/2022: Trial's existence confirmed by Chang Gung Medical Foundation IRB