Clinical trial NCT04858854: Effect of Broccoli Sprout Extract in Patients With Chronic Kidney Disease With Diabetes Type 2
Official title: Effect of Broccoli Sprout Extract in Patients With Chronic Kidney Disease With Diabetes Type 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease Stage 3B
Chronic Kidney Disease stage4
Diabetes Mellitus, Type 2
Keywords: Sulforaphane
Nutrition
Glucose control
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Lantmännen
First posted: 2021-04-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicentre randomized double-blinded controlled trial lasting 20 weeks with two study periods. The first 12 weeks will constitute a treatment period with BSE (BSE group) or placebo (Control group) depending on the randomization of the group allocation. After that, patients from both groups will be followed for another eigth weeks, called post-study observational period.
Primary purpose: TREATMENT

Brief summary: This research project aims to test if sulforaphane, administered as broccoli sprout extract (BSE) can ameliorate glucose control in adult patients with chronic kidney disease (CKD) and DM 2 with GFR \> 15 \< 45 ml/min/1.73 m2. The glucose control will be evaluated by the oral glucose tolerance test. Moreover, as a secondary aim, we will investigate the role of sulforaphane in improving other signs of metabolic derangements present in this group of patients, including oxidate stress, proteinuria, inflammation and a decrease in the production of uremic toxins from the gut microbiota. This a multicentre randomized double-blinded controlled trial including 100 adult patients with CKD and glomerular filtration rate (GFR) between 15 and 29 ml/min/1.73m2, DM type 2, age \> 18 years old. Patients will be randomized into BSE group or Placebo group. Both groups will be followed for 20 weeks: The first 12 weeks patients will receive the BSE or Placebo and, the next 8 weeks, both groups will be followed with no intervention to observe the changes in the primary and secondary outcomes. Patients randomized to BSE Group will receive 50 µmmol/day of sulforaphane administered as BSE (Lantmännen®) from week 0 to week 4. If no side-effects are reported, the sulforaphane dose will increase to 100 µmmol/day from week 5 to week 8 and in the absence of side-effects, the dose will increase to 150 µmmol/day from week 9 to week 12. Blood and urine samples and OGTT (in non-insulin dependent patients) will be performed at week 0, 12 and 20. On week 4 and 8 blood drawn for partial exam will be performed. The BSE and the placebo (maltodextrin sprayed with copper-chlorophyllin) will be administered as powder provided in a double-blind manner as dry mixtures in sealed portion size bags of similar shape and size. Randomization will be done using a computer-based block randomization algorithm. Comparisons between the primary and secondary studied variables will be done with two-way analysis of variance (ANOVA) with repeated measures for normally distributed variables. Variables that can interfere with the glycemic control, such as changes in the dosage of hypoglicemiants agents and insulin during the intervention will be controlled in the analysis. Those non-normally distributed will be log transformed aiming to normalize the distribution. All test will consider a P\<0.05 for statistical significance. The software Stata will be used for the statistical analysis.


Eligibility criteria: Inclusion Criteria:

* Patients with a GFR 15-45 ml/min/1.73 m2, DM type 2, age \>18 years old, able to read and understand Swedish.

Exclusion Criteria:

* Use of metformin, use of warfarin, levels of ASAT, ALAT more than three times the upper limit at screening or at any subsequent visit, kidney transplantation, inflammatory bowel disease, celiac disease, malignant diseases (except skin basalioma) in the previous 3 years, and any other condition that the treating doctor believes is contraindicated; allergy to broccoli; participation in another clinical trial which may affect the outcome of the present study; not to understand the study information.

Primary outcomes:
measure: Fasting serum glucose
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: C-reactive protein (CRP)
timeFrame: Baseline, Week 12 and Week 20
measure: Interleukin-6 (IL6)
timeFrame: Baseline, Week 12 and Week 20
measure: Tumor necrosis alpha (TNF)
timeFrame: Baseline, Week 12 and Week 20
measure: Interleukin 10
timeFrame: Baseline, Week 12 and Week 20
measure: Advanced oxidation protein products (AOPP)
timeFrame: Baseline, Week 12 and Week 20
measure: 8-hydroxydeoxyguanosine (8-OHdG)
timeFrame: Baseline, Week 12 and Week 20
measure: Urinary albumin creatinine ratio (ACR)
timeFrame: Baseline, Week 12 and Week 20
measure: Indoxyl-sulfate (IS)
timeFrame: Baseline, Week 12 and Week 20
measure: Trimethylamine N-oxide (TMAO)
timeFrame: Baseline, Week 12 and Week 20
measure: P-cresyl sulfate (IPC)
timeFrame: Baseline, Week 12 and Week 20
measure: Oral glucose tolerance test
timeFrame: Baseline, Week 12 and Week 20
measure: Fasting HbA1c
timeFrame: Baseline, Week 12, Week 20 and week 20
measure: Fasting insulin
timeFrame: Baseline, Week 4, Week 8, Week 12 and Week 20
Other outcomes:
Locations:
city: Gävle
country: Sweden
facility: Gävle Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Linköping
country: Sweden
facility: Linköpings universitet
city: Lund
country: Sweden
facility: Skånes University Hospital Sus
city: Malmö
country: Sweden
facility: Skånes universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Stockholm
country: Sweden
facility: Danderyds sjukhus AB
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
city: Varberg
country: Sweden
facility: Hallands Hospital Varberg
city: Västervik
country: Sweden
facility: Västervikssjukhus
city: Västerås
country: Sweden
facility: Västmanlands Hospital Västerås
Study officials:
affiliation: Karolinska Institutet
name: Peter x Stenvinkel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Carla Avesani, PhD
role: STUDY_CHAIR
affiliation: Karolinska Institutet
name: Marie Evans, MD
role: STUDY_DIRECTOR
References: