The primary aim of the study is to improve microvascular endothelial health after 3 months expressed by the Microvascular Healt Index, using a non-invasive imaging technique, upon two different dietary interventions compared to the placebo. The…
ID
Source
Brief title
Condition
- Diabetic complications
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is an improvement of the Microvascular Health index in the
diet group compared to the placebo group, and in the food supplement group
compared to the placebo group, after 3 months of the intervention.
Secondary outcome
Secondary endpoints: reduce albuminuria, decrease inflammation (urinary
heparanase and MCP-1 expression, serum CRP and MCP-1 levels), reduce
occurrence of specific urinary HS domains, improve metabolic parameters;
fasting glucose, HbA1c, C-peptide, IGF-1, total cholesterol, LDL cholesterol,
HDL cholesterol, and triglycerides serum levels, waist circumference,
waist-to-hip ratio, body weight and systolic blood pressure after 3 months of
the fasting mimicking diet and after 3 months of the food supplement. The
legacy effect of the interventions is also determined, 3 months after stopping
with the intervention.
Background summary
Micro- and macrovascular complications are the pathological hallmarks of
diabetes mellitus, with diabetic nephropathy as one of the most serious
microvascular complications. South Asians have a high incidence of type 2
diabetes and a higher change to progress to end-stage renal disease than West
European patients, which may be due to a higher sustained systemic and
glomerular inflammation. The endothelial glycocalyx, covering endothelial
cells, is essential for maintaining vascular homeostasis. In the diabetic
environment, impairment of the glycocalyx can be induced by invading
macrophages which excrete the glycocalyx degrading enzyme heparanase and its
activator cathepsin L. In the glomerulus, impairment of the glycocalyx results
in increased permeability for albumin alongside renal and vascular
inflammation. SDF-imaging is a non-invasive technique to visualize the
endothelial glycocalyx and obtains parameters that reflect the microvascular
endothelial status, combined in the Microvascular Health Index (MHI). Here we
investigate if dietary interventions, which either provide the nutritional
building blocks to support and maintain the endothelial glycocalyx or reduce
the overall inflammatory burden, can aid in restoration of the glomerular
endothelial glycocalyx and in turn result in a reduction of albuminuria and
further delay, or prevent renal damage.
Study objective
The primary aim of the study is to improve microvascular endothelial health
after 3 months expressed by the Microvascular Healt Index, using a non-invasive
imaging technique, upon two different dietary interventions compared to the
placebo. The secondary objective is to monitor the dietary effects after 3
months on systemic inflammation, metabolic parameters and albuminuria. Finally,
we aim to determine new urinary heparan sulphate fragment biomarkers which can
be related to specific glomerular extracellular heparanase activity, a possible
central player in local glomerular damage and renal inflammation.
Study design
A randomized, placebo controlled, 3-arm intervention field study for 3 months
with additional 3 month follow up measurements.
Intervention
One group receives a monthly 5-day fasting mimicking diet for 3 consecutive
months, one group receives daily 4 capsules of a food supplement and one group
receives daily 4 placebo capsules, all for 3 consecutive months.
Study burden and risks
Eligible patients are randomly assigned to the fasting mimicking diet, food
supplement or placebo arm. At baseline, after 3 months and at 6 months, the MHI
is measured by non-invasive SDF imaging of the microcirculation under the
tongue, and blood and urine samples are collected. In the FMD arm, dosages of
the hypoglycaemic drugs are adapted during the 5 days of the diet prevent
hypoglycaemia. Glucose monitoring is done during the diet and at the end of
each month in all intervention arms through a finger prick blood sample.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
1. South Asian patient with diabetes mellitus type 2.
2. Female or male, aged between 18 and 75 years.
3. Body Mass Index *18.5.
4. CKD-EPI >45 ml/min/1.73m² at baseline.
5. Proven microalbuminuria defined as albumin/creatinine ratio *0.3 and <30
mg/mmol (single portion) or 3-300 mg albumin per day (24 hours urine
collection) in the last twelve months.
6. Blood pressure of *180 mmHg with standard antihypertensive care.
7. Treatment with hypoglycaemic drugs: metformin, sulphonylureas and/or
insulin.
8. Subject is willing to participate in the study, must be able to give
informed consent and the consent must be obtained prior to any study procedure.
9. Patients must be able to adhere to the study visit schedule and protocol
requirements.
10. If female and of child-bearing age, patients must be non-pregnant,
non-breastfeeding, and use adequate contraception.
Exclusion criteria
1. Any concurrent illness, disability or clinically significant abnormality
that may, as judged by the investigator, affect the interpretation of clinical
efficacy or safety data or prevent the subject from safely completing the
assessments required by the protocol.
2. Non-diabetic renal disease e.g. known polycystic kidney disease.
3. Use of LMW heparin and/or immunosuppressive drugs.
4. Significant food allergies for galactose, nuts, soy, tomato, corn, grape,
melon and artichoke, which would make the subject unable to consume the food
provided.
5. Signs of active infection or autoimmune disease, requiring systemic
treatment.
6. A psychiatric, addictive or any disorder that compromises ability to give
truly informed consent for participation in this study.
7. Malignancy (including lymphoproliferative disease) within the past 2-5 years
(except for squamous or basal cell carcinoma of the skin that has been treated
with no evidence of recurrence).
8. Use of any other investigational drug.
9. Patient has enrolled another clinical trial within last 4 weeks.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 |
|---|---|
| CCMO | NL63186.058.17 |