INITIATE: Effect of Broccoli Sprout Extract in Patients With Chronic Kidney Disease With Diabetes Type 2

Sponsor

Karolinska Institutet (Other)

Overall Status

Recruiting

CT.gov ID

NCT04858854

Collaborator

Lantmännen (Other)

100

Enrollment

Locations

Arms

10.6

Anticipated Duration (Months)

12.5

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease Stage 3B Chronic Kidney Disease stage4 Diabetes Mellitus, Type 2	Other: Sulforaphane, administered as Broccoli sprout extract	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Effect of Broccoli Sprout Extract in Patients With Chronic Kidney Disease With Diabetes Type 2

Actual Study Start Date :

Oct 10, 2021

Anticipated Primary Completion Date :

Aug 30, 2022

Anticipated Study Completion Date :

Aug 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: BSE group (Broccoli sprout group) The BSE Group will receive 50 µmmol/day of sulforaphane administered by 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.	Other: Sulforaphane, administered as Broccoli sprout extract Patients will randomized to BSE or Control Group. The group BSE will receive the sulforaphane, administered as broccoli sprout extract for 12 weeks. The dose will increase every four weeks if no side-effects are reported (50 µmmol/day; 100 µmmol/day and 150 µmmol/day, respectivelly). The Control group will receive a placebo (maltodextrin sprayed with copper-chlorophyllin) for the same period (12 weeks). The BSE/placebo will be administered as powder provided in 10 ml of water in the morning in a double-blind manner as dry mixtures in sealed portion size bags of similar shape and size.
Placebo Comparator: Control group The Control Group will receive a placebo (maltodextrin sprayed with copper-chlorophyllin) for 12 weeks.	Other: Sulforaphane, administered as Broccoli sprout extract Patients will randomized to BSE or Control Group. The group BSE will receive the sulforaphane, administered as broccoli sprout extract for 12 weeks. The dose will increase every four weeks if no side-effects are reported (50 µmmol/day; 100 µmmol/day and 150 µmmol/day, respectivelly). The Control group will receive a placebo (maltodextrin sprayed with copper-chlorophyllin) for the same period (12 weeks). The BSE/placebo will be administered as powder provided in 10 ml of water in the morning in a double-blind manner as dry mixtures in sealed portion size bags of similar shape and size.

Arm

Intervention/Treatment

Active Comparator: BSE group (Broccoli sprout group)

The BSE Group will receive 50 µmmol/day of sulforaphane administered by 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.

Other: Sulforaphane, administered as Broccoli sprout extract

Patients will randomized to BSE or Control Group. The group BSE will receive the sulforaphane, administered as broccoli sprout extract for 12 weeks. The dose will increase every four weeks if no side-effects are reported (50 µmmol/day; 100 µmmol/day and 150 µmmol/day, respectivelly). The Control group will receive a placebo (maltodextrin sprayed with copper-chlorophyllin) for the same period (12 weeks). The BSE/placebo will be administered as powder provided in 10 ml of water in the morning in a double-blind manner as dry mixtures in sealed portion size bags of similar shape and size.

Placebo Comparator: Control group

The Control Group will receive a placebo (maltodextrin sprayed with copper-chlorophyllin) for 12 weeks.

Other: Sulforaphane, administered as Broccoli sprout extract

Outcome Measures

Primary Outcome Measures

Fasting serum glucose [Baseline, Week 12]
Change in fasting serum glucose from baseline at week 12

Secondary Outcome Measures

C-reactive protein (CRP) [Baseline, Week 12 and Week 20]
Inflammatory marker
Interleukin-6 (IL6) [Baseline, Week 12 and Week 20]
Inflammatory marker
Tumor necrosis alpha (TNF) [Baseline, Week 12 and Week 20]
Inflammatory marker
Interleukin 10 [Baseline, Week 12 and Week 20]
Inflammatory marker
Advanced oxidation protein products (AOPP) [Baseline, Week 12 and Week 20]
Oxidative stress
8-hydroxydeoxyguanosine (8-OHdG) [Baseline, Week 12 and Week 20]
Oxidative stress
Urinary albumin creatinine ratio (ACR) [Baseline, Week 12 and Week 20]
Proteinuria
Indoxyl-sulfate (IS) [Baseline, Week 12 and Week 20]
Uremic toxins
Trimethylamine N-oxide (TMAO) [Baseline, Week 12 and Week 20]
Uremic toxins
P-cresyl sulfate (IPC) [Baseline, Week 12 and Week 20]
Uremic toxins
Oral glucose tolerance test [Baseline, Week 12 and Week 20]
Performed in patients not using insulin at the local participating Hospital Chemical
Fasting HbA1c [Baseline, Week 12, Week 20 and week 20]
Fasting HbA1c
Fasting insulin [Baseline, Week 4, Week 8, Week 12 and Week 20]
Fasting insulin

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Sahlgrenska Universitetssjukhuset	Göteborg	Sweden	41345
2	Linköpings universitet	Linköping	Sweden	58183
3	Skånes universitetssjukhus	Malmö	Sweden	20502
4	Karolinska Institutet	Stockholm	Sweden	14134
5	Danderyds sjukhus AB	Stockholm	Sweden	18288
6	Norrlands Universitetssjukhus	Umeå	Sweden	90185
7	Akademiska sjukhuset	Uppsala	Sweden	75185
8	Västervikssjukhus	Västervik	Sweden	59333