This study has been transitioned to CTIS with ID 2023-506082-60-00 check the CTIS register for the current data. The objective of this study is to investigate the mechanism(s) of action of tirzepatide in the kidney, in participants who are…
ID
Source
Brief title
Condition
- Other condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Renal disorders (excl nephropathies)
Synonym
Health condition
metabolism and nutrition disorders
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Following parameters will be determined to compare the effect of tirzepatide
MTD (10 or 15 mg) once a week and placebo after 52 weeks of treatment in
participants with and without T2D:
- kidney oxygenation
Secondary outcome
Following parameters will be determined to compare the effect of tirzepatide
MTD (10 or 15 mg) once a week and placebo after 52 weeks of treatment in
participants with and without T2D:
- body weight
- renal sinus fat
- renal fat content
- renal blood flow
- kidney apparent diffusion coefficient
- glomerular filtration rate
- urinary albumin excretion
- urine albumin-to-creatinine ratio
- kidney inflammation
- kidney oxidative metabolism
- fractional urinary sodium excretion
- 24-hour sodium excretion
- waist circumference
- blood pressure
- heart rate
- HbA1c and CRP
- lipids
- health-related quality of life
- mitochondrial function
Background summary
The worldwide epidemic of obesity has resulted in an increasing incidence of
obesity-related comorbidities, including chronic kidney disease. Treatment
options to delay progression to end-stage renal disease in people with CKD are
limited, and there is a growing, unmet need to provide people with obesity and
CKD with a safe and effective therapy.
Tirzepatide, a novel, dual GLP-1/GIP receptor agonist, has demonstrated robust
efficacy activity in lowering blood glucose and inducing weight loss.
Study objective
This study has been transitioned to CTIS with ID 2023-506082-60-00 check the CTIS register for the current data.
The objective of this study is to investigate the mechanism(s) of action of
tirzepatide in the kidney, in participants who are overweight or living with
obesity and coexisting CKD, with and without T2D, to inform potential future
kidney outcomes studies.
Study design
Study I8F-MC-GPIG is a Phase 2b, mechanistic, multicenter, randomized,
parallel, placebocontrolled, double-blinded, 52-week study that will
investigate the effects on the kidney of tirzepatide (MTD 10 or 15 mg QW),
compared with placebo, in participants who are overweight or living with
obesity and coexisting CKD, with and without T2D. The pharmacological treatment
will be combined with a lifestyle intervention, consisting of a reduced-calorie
diet, and increased physical activity.
Intervention
tirzepatide Maximal Tolerated Dose (10 or 15 mg) or placebo.
Tirzepatide or placebo treatment duration is 52 weeks in total: up to 20-week
dose escalation period and a 32-week treatment period.
Tirzepatide or matching placebo will be administered weekly by single-dose pen.
Pharmacological treatment will be combined with a lifestyle intervention,
consisting of a reduced-calorie diet, and increased physical activity.
Study burden and risks
- Tirzepatide has been associated with following adverse events: feeling sick
to the stomach; loose or frequent stools; vomiting; loss of appetite;
indigestion; heartburn; feeling tired; fatigue; hard or infrequent stools;
passing gas; bloating; belching; stomach pain or discomfort; low blood sugar;
injections site reaction (such as redness, irritation, itching, swelling or
rash).
- There may be some discomfort from the measurements during the study. For
example: taking a blood sample can be a little painful. Subjects will be
exposed to some level of radiation due to PET scan. MRI or PET/CT scan can be
uncomfortable.
- Taking part in the study will cost extra time and subjects have to go to the
research facility for study visits.
- Subjects have to comply with the study agreements such as keep diabetes
diary, keep study drug log, follow diet and lifestyle advice.
- GFR will be measured using iohexol, which might cause allergic
reactions or hypersensitivity reactions in some people.
- If subjects have type 2 diabetes, they may experience worsening of their
blood sugar levels and related symptoms if they receive placebo. The study
doctor will explain to them what measures to take to manage it.
- Participants with T2D may experience discomfort during eye exams.
Island House, Eastgate Business Park, Little Island na
Cork Co.
NL
Island House, Eastgate Business Park, Little Island na
Cork Co.
NL
Listed location countries
Age
Inclusion criteria
1. Participants without diabetes must have HbA1c of <= 6.5 %.
2. Participants with diabetes must have HbA1c >= 7 % to <= 10.5 % at screening
visit.
3. Participants must be at least 18 years of age or the legal age of consent in
the jurisdiction where the study is taking place.
4. Participants must have a BMI >= 27kg/cm2 at screening visit.
5. Participants must be diagnosed with CKD having a eGFR >=30 to <= 60 mL/min1.73
m2 or eGFR >= 30 to 75 mL/min/1.73 m2 if UACR > 30 mg/g, calculated by CKD-EPI
equation, as determined by central labs at screening visit.
6. Participants must have been receiving an ACE or ARBi that is considered the
maximal appropriate dose by the investigator for treatment of CKD or
hypertension (unless patient has low blood pressure or hypotension). The dose
must have been unchanged for 30 days before screening visit.
Exclusion criteria
For participants with T2D the following exclusion criteria apply:
1. Participants have a history of proliferative diabetic retinopathy or
diabetic macular edema or non-proliferative edema or non-proliferative diabetic
retinopathy that requires acute treatment.
2. Participants who have uncontrolled diabetes (such as diabetic ketoacidosis)
at screening or randomization, in the judgement of the physician.
For participants without T2D the following exclusion criteria apply:
3. Have T1DM or a history of ketoacidosis ot hypersmolar state/coma
4. Have self reported change in body weight >5kgs within the 90 days prior to
screening visit
5. Have had or plan to have surgical treatment for obesity (excluding
liposuction or abdominoplasty if performed >1 year prior to screening)
6. Have or plan to have endoscopic and or device based therapy for obesity or
have had device removal within the last 180 days e.g. mucosal ablation, gastric
artery embolization, intragastric balloon and duodenal jejunal bypass device.
7. Have eGFr < 30 mL/min/1.73 m2 calculated by CKD-EPI equation.
8. Have a history of unstable or rapidly progressing renal disease according to
investigator judgement.
9. Have a history of a congenital or hereditary kidney disease, like polycystic
kidney disease or congenital urinary tract malformations
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506082-60-00 |
| EudraCT | EUCTR2021-005273-47-NL |
| CCMO | NL81303.056.22 |