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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Chronic Kidney Disease stage4; Chronic Kidney Disease Stage 3B
• Intervention / Treatment: Other: Sulforaphane, administered as Broccoli sprout extract

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Gävle, Sweden, 80187
    • Gävle Hospital
  • Göteborg, Sweden, 41345
    • Sahlgrenska Universitetssjukhuset
  • Linköping, Sweden, 58183
    • Linköpings Universitet
  • Lund, Sweden, 22185
    • Skånes University Hospital Sus
  • Malmö, Sweden, 20502
    • Skanes universitetssjukhus
  • Stockholm, Sweden, 18288
    • Danderyds Sjukhus AB
  • Stockholm, Sweden, 14134
    • Karolinska Institutet
  • Umeå, Sweden, 90185
    • Norrlands Universitetssjukhus
  • Uppsala, Sweden, 75185
    • Akademiska Sjukhuset
  • Varberg, Sweden, 43281
    • Hallands Hospital Varberg
  • Västervik, Sweden, 59333
    • Västervikssjukhus
  • Västerås, Sweden, 72189
    • Västmanlands Hospital Västerås

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting serum glucose	Change in fasting serum glucose from baseline at week 12	Baseline, Week 12

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Lantmännen
• Investigators: Principal Investigator: Peter x Stenvinkel, MD, Karolinska Institutet; Study Chair: Carla Avesani, PhD, Karolinska Institutet; Study Director: Marie Evans, MD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2021
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): May 18, 2023

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 23, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Glucose control; Nutrition; Sulforaphane
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Anticarcinogenic Agents; Sulforaphane
• Other Study ID Numbers: 2020-06468

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No