DIALYSIS-TIR Study

• ClinicalTrials.gov Identifier: NCT06042153
• Recruitment Status: Not yet recruiting
• First Posted: September 18, 2023
• Last Update Posted: September 18, 2023
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: University of North Carolina, Chapel Hill
• Information provided by (Responsible Party): Ildiko Lingvay, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes; End Stage Renal Disease on Dialysis	Drug: Semaglutide; Drug: Placebo	Phase 4

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 157 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a multi-center, randomized, double-blind, parallel-group, placebo-controlled, trial comparing semaglutide subcutaneously weekly versus matched placebo
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The randomization and each dispensation will be performed by blinded study staff using an electronic system coded with the randomization code, to ensure all study personnel remains blinded.
• Primary Purpose: Treatment
• Official Title: Semaglutide for Dialysis-Treated Patients - a Glucose Time in Range Study- DIALYSIS-TIR Study
• Estimated Study Start Date: December 2023
• Estimated Primary Completion Date: September 2025
• Estimated Study Completion Date: September 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in TIR (70-180 mg/dl) [ Time Frame: Baseline, 52 weeks ]
   Measured in percentage by Continuous glucose monitor (CGM)

Secondary Outcome Measures :

1. Change in Time in high range (180-250 mg/dl) [ Time Frame: Baseline, 52 weeks ]
   Measured in percentage by Continuous glucose monitor (CGM)
2. Change in Time in very high range (>250 mg/dl) [ Time Frame: Baseline, 52 weeks ]
   Measured in percentage by Continuous glucose monitor (CGM)
3. Change in Time in low range (54-69 mg/dl) [ Time Frame: Baseline, 52 weeks ]
   Measured in percentage by Continuous glucose monitor (CGM)
4. Change in Time in very low range (<54 mg/dl) [ Time Frame: Baseline, 52 weeks ]
   Measured in percentage by Continuous glucose monitor (CGM)
5. Proportion of participants with TIR 70-180 mg/dl for 70% of the day [ Time Frame: 52 weeks ]
   Measured in percentage by CGM
6. Proportion of participants with TIR 70-180 mg/dl with more than equal to 5% improvement from baseline [ Time Frame: 52 weeks ]
   Measured in percentage by CGM
7. Proportion of participants with Time below range <70 mg/dL for <4% of each day [ Time Frame: 52 weeks ]
   Measured in percentage by CGM
8. Proportion of participants with Time below range <54 mg/dL for <1% of each day [ Time Frame: 52 weeks ]
   Measured in percentage by CGM
9. Proportion of participants with Time above range >180 mg/dL for <25% of each day [ Time Frame: 52 weeks ]
   Measured in percentage by CGM
10. Change in haemoglobin A1c (HbA1c) [ Time Frame: Baseline, 52 weeks ]
    Measured in percentage
11. Total daily dose of insulin [ Time Frame: 52 weeks ]
    Measured as units/day
12. Number of oral glucose lowering agents [ Time Frame: 52 weeks ]
    Measured as count
13. 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% [ Time Frame: 52 weeks ]
    Measured in percentage
14. Proportion of participants with mean glucose <154 mg/dL and <1% time below range <54 mg/dL [ Time Frame: 52 weeks ]
    Measured in percentage
15. Number of participants with Severe hypoglycemia [ Time Frame: 52 weeks ]
    Measured in count
16. Change in body weight [ Time Frame: Baseline, 52 weeks ]
    Measured in kilograms
17. Change in waist circumference [ Time Frame: Baseline, 52 weeks ]
    Measured in centimeters
18. Change in percentage total body fat [ Time Frame: Baseline, 52 weeks ]
    Measured in percentage
19. Change in percentage lean mass [ Time Frame: Baseline, 52 weeks ]
    Measured in percentage
20. Change in Inter-dialysis weight gain [ Time Frame: Baseline, 52 weeks ]
    Measured in kilograms
21. Number of participants hospitalized [ Time Frame: 52 weeks ]
    Measured in count
22. Total number of days spent in hospital [ Time Frame: 52 weeks ]
    Measured in count
23. Total score of Diabetes Treatment Satisfaction questionnaire [ Time Frame: 52 weeks ]
    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.
24. Total score of EQ-5D-5L [ Time Frame: 52 weeks ]

    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

25. Total score of Kidney disease QoL short form [ Time Frame: 52 weeks ]
    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.").

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Contacts

Contact: Marielle Berger-Nagele, MS; 214-648-2363; marielle.berger-nagele@utsouthwestern.edu

Contact: Ileana Cuevas, PhD; 214-648-2321; ileana.cuevas@utsouthwestern.edu

Locations

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Contact: Alex Kass, MSN, MBA, RN 984-974-3009 alex_kass@med.unc.edu

Contact: Klara Klein, MD 9849743004 klara_klein@med.unc.edu

Principal Investigator: Klara Klein, MD

Sponsors and Collaborators

University of Texas Southwestern Medical Center

University of North Carolina, Chapel Hill

Investigators

• Principal Investigator: Ildiko Lingvay, MD, MPH, MSCS; UT Southwestern Medical Center

More Information

• Responsible Party: Ildiko Lingvay, Professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT06042153
• Other Study ID Numbers: STU-2022-0786
• First Posted: September 18, 2023
• Last Update Posted: September 18, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Kidney Failure, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes