DIALYSIS-TIR Study

Semaglutide for Dialysis-Treated Patients - a Glucose Time in Range Study- DIALYSIS-TIR Study

This study will look at control of blood sugar levels in persons with type 2 diabetes mellitus currently on chronic dialysis. Researchers will compare blood sugar levels in people taking semaglutide to people taking "dummy" medicine. The treatment participants get will be decided randomly.

Participants will need to inject the study medication once a week. The study will last for 1 year and a month. Participants will be asked to wear a sensor that measures blood sugar levels for a period of 10 days at five different time points during the study.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes; End Stage Renal Disease on Dialysis
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo

Detailed Description

The researchers also have a Data Safety Monitoring Plan in place.

• Study Type: Interventional
• Enrollment (Estimated): 157
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marielle Berger-Nagele, MS; Phone Number: 214-648-2363; Email: marielle.berger-nagele@utsouthwestern.edu
• Study Contact Backup: Name: Ileana Cuevas, PhD; Phone Number: 214-648-2321; Email: ileana.cuevas@utsouthwestern.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Not yet recruiting
      • University of North Carolina
      • Contact: Alex Kass, MSN, MBA, RN; Phone Number: 984-974-3009; Email: alex_kass@med.unc.edu
      • Contact: Klara Klein, MD; Phone Number: 9849743004; Email: klara_klein@med.unc.edu
      • Principal Investigator: Klara Klein, MD
  • Texas
    • Dallas, Texas, United States, 75224
      • Recruiting
      • Davita UT Southwestern - Oak Cliff
      • Contact: Marielle Berger-Nagele, MS; Email: marielle.berger-nagele@utsouthwestern.edu
      • Contact: Ileana Cuevas, PhD; Email: ileana.cuevas@utsouthwestern.edu
    • Dallas, Texas, United States, 75228
      • Not yet recruiting
      • DaVita UT Southwestern - East Dallas
      • Contact: Marielle Berger-Nagele, MS; Phone Number: 2146482363; Email: marielle.berger-nagele@utsw.edu
      • Contact: Ileana Cuevas, PhD; Phone Number: 2146482321; Email: ileana.cuevas@utsouthwestern.edu
      • Principal Investigator: Ildiko Lingvay, MD, MPH, MSCS
    • Dallas, Texas, United States, 75240
      • Not yet recruiting
      • DaVita UT Southwestern - Preston
      • Contact: Marielle Berger-Nagele, MS; Phone Number: 2146482363; Email: marielle.berger-nagele@utsw.edu
      • Contact: Ileana Cuevas, PhD; Phone Number: 2146482321; Email: ileana.cuevas@utsouthwestern.edu
      • Principal Investigator: Ildiko Lingvay, MD, MPH, MSCS
    • Irving, Texas, United States, 75062
      • Recruiting
      • DaVita UT Southwestern - Irving
      • Contact: Marielle Berger-Nagele, MS; Email: marielle.berger-nagele@utsouthwestern.edu
      • Contact: Ileana Cuevas, PhD; Email: ileana.cuevas@utsouthwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to provide informed consent before any trial-related activities. Trial-related activities are any procedures that are carried out as a part of trial, including activities to determine suitability for the trial.
2. Male or female Adults (age > 18 years at the time of signing the consent)
3. Type 2 diabetes mellitus diagnosed > 6 months prior to screening
4. On current chronic treatment with Hemodialysis or Peritoneal dialysis for > 6 months prior to screening
5. Current treatment with any glucose lowering pharmacotherapy, at a stable dose for at least 30 days. DPP-4 Inhibitors will be allowed at study entry and will be stopped at randomization.
6. Minimum of 80% valid data on the 10-day Continuous Glucose Monitor download
7. Time in Range 15 to 60%

Exclusion Criteria:

1. BMI < 23 kg/m2 at screening
2. Current (within the past 90 days of screening) use of any GLP-1 RA
3. Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia type 2
4. Known or suspected hypersensitivity to GLP-1 RA (trial medication(s), excipients, or related products)
5. Pregnant, breast-feeding or the intention of becoming pregnant, or not using effective contraceptive measures
6. Active weight loss, defined as weight loss of >5% of body weight in the past 3 months
7. Current participation in other interventional trials or last dose of any investigational product within 4 half- lives at the time of randomization
8. Any medical condition which in the judgement of the investigator precludes safe participation in the trial (includes, but not limited to active neoplasm, severe heart failure, recent cardiovascular event, severe frailty, planned cardiac or vascular surgeries on the day of screening etc)
9. If weight loss is not desired by the participant, or if the provider or investigator considers intentional weight loss to be detrimental to the health of the participant
10. Other or secondary forms of diabetes (like type 1 diabetes, pancreatogenic diabetes mellitus, MODY, LADA, drug induced, etc.)
11. Current diagnosis of gastroparesis or enteropathywhich in the opinion of investigator precludes safe treatment with GLP-1 RA.
12. Hypoglycaemia unawareness, or history of frequent or severe hypoglycaemia (in the opinion of the investigator)
13. Personal history of chronic pancreatitis, or acute pancreatitis within 180 days of screening
14. Known current uncontrolled or unstable retinopathy (by medical history)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - Semaglutide; Participants will receive semaglutide as an adjunct to standard-of-care.	Drug: Semaglutide; Semaglutide will be injected into a skin fold, in the stomach, thigh or upper arm once a week at the same day of the week (to the extent possible) throughout the trial. Subjects will start semaglutide treatment at 0.25 mg; dose will gradually be increased every 4 weeks up to 1.0 mg.
Placebo Comparator: Arm 2- Placebo; Participants will receive placebo (semaglutide) as an adjunct to standard-of-care.	Drug: Placebo; Placebo will be injected into a skin fold, in the stomach, thigh or upper arm once a week at the same day of the week (to the extent possible) throughout the trial. Participants will receive placebo at an equivalent dose to semaglutide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in TIR (70-180 mg/dl)	Measured in percentage by Continuous glucose monitor (CGM)	Baseline, 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Time in high range (180-250 mg/dl)	Measured in percentage by Continuous glucose monitor (CGM)	Baseline, 52 weeks
Change in Time in very high range (>250 mg/dl)	Measured in percentage by Continuous glucose monitor (CGM)	Baseline, 52 weeks
Change in Time in low range (54-69 mg/dl)	Measured in percentage by Continuous glucose monitor (CGM)	Baseline, 52 weeks
Change in Time in very low range (<54 mg/dl)	Measured in percentage by Continuous glucose monitor (CGM)	Baseline, 52 weeks
Proportion of participants with TIR 70-180 mg/dl for 70% of the day	Measured in percentage by CGM	52 weeks
Proportion of participants with TIR 70-180 mg/dl with more than equal to 5% improvement from baseline	Measured in percentage by CGM	52 weeks
Proportion of participants with Time below range <70 mg/dL for <4% of each day	Measured in percentage by CGM	52 weeks
Proportion of participants with Time below range <54 mg/dL for <1% of each day	Measured in percentage by CGM	52 weeks
Proportion of participants with Time above range >180 mg/dL for <25% of each day	Measured in percentage by CGM	52 weeks
Change in haemoglobin A1c (HbA1c)	Measured in percentage	Baseline, 52 weeks
Total daily dose of insulin	Measured as units/day	52 weeks
Number of oral glucose lowering agents	Measured as count	52 weeks
Proportion of participants with >10 points improvement in % TIR 70-180 mg/dL without an increase in time below range <54 mg/dL of >0.5%	Measured in percentage	52 weeks
Proportion of participants with mean glucose <154 mg/dL and <1% time below range <54 mg/dL	Measured in percentage	52 weeks
Number of participants with Severe hypoglycemia	Measured in count	52 weeks
Change in body weight	Measured in kilograms	Baseline, 52 weeks
Change in waist circumference	Measured in centimeters	Baseline, 52 weeks
Change in percentage total body fat	Measured in percentage	Baseline, 52 weeks
Change in percentage lean mass	Measured in percentage	Baseline, 52 weeks
Change in Inter-dialysis weight gain	Measured in kilograms	Baseline, 52 weeks
Number of participants hospitalized	Measured in count	52 weeks
Total number of days spent in hospital	Measured in count	52 weeks
Total score of Diabetes Treatment Satisfaction questionnaire	Patient reported outcomes is assessed by Diabetes Treatment Satisfaction Score questionnaire which assesses patient satisfaction with diabetes treatment. It is composed of eight questions, each of which is scored by patients on a scale ranging from zero (e.g., "very dissatisfied", "very inconvenient") to six (e.g., "very satisfied", "very convenient"). Treatment satisfaction is assessed as the sum of the scores of the six questions on the first factor, with a higher score indicating higher treatment satisfaction.	52 weeks
Total score of EQ-5D-5L	The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. Possible scores range from 0-100, where higher score indicate better outcome	52 weeks
Total score of Kidney disease QoL short form	The KDQOL-SF is a self-report measure developed for individuals with kidney disease and those on dialysis. It is a shorter version of a measure developed by the same authors. It includes 43 kidney disease-targeted items, such as the effects of the disease of activities of daily living, work status, and social interaction, and 36 items that provide a measure of physical and mental health, and 1 overall health rating item ranging from 0 ("worst possible health") to 10 ("best possible health.").	52 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Ildiko Lingvay, MD, MPH, MSCS, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: September 11, 2023
• First Submitted That Met QC Criteria: September 11, 2023
• First Posted (Actual): September 18, 2023

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 11, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: STU-2022-0786

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No