Clinical Trial With Broccoli Sprout Extract to Patients With Type 2 Diabetes

Phase 2

Completed

• Conditions: Diabetes Mellitus, Non-Insulin-Dependent
• Interventions: Drug: Placebo; Drug: sulforaphane

• Registration Number: NCT02801448
• Lead Sponsor: Anders Rosengren, MD PhD

Brief Summary

Type 2 diabetes (T2D) results from a combination of insufficient insulin secretion from pancreatic islets and insulin resistance of target cells. The investigators have extensive pre-clinical data suggesting that BSE through its high content of the isothiocyanate sulforaphane improves hepatic insulin sensitivity. BSE as a dietary supplement could therefore benefit both patients with T2D and individuals at risk for the disease. BSE-containing sulforaphane is suggested to activate Nuclear factor-like 2 (NRF2). The investigators aim to study the clinical effect of using BSE as a dietary supplement on glucose tolerance and insulin sensitivity.

Detailed Description

Sulforaphane binds to Keap1 in the cytosol, leading to nuclear translocation of this transcription factor. In the nucleus NRF2 induces the expression of a large number of anti-oxidative genes. Sulforaphane is contained at high concentration in broccoli sprout extracts (BSE). Human studies have been conducted using broccoli sprout products without complication. It is being tested for the treatment or prevention of cancer and inflammatory diseases in \~30 clinical trials without any serious adverse events reported. The low toxicity makes BSE ideal as a dietary supplement for preventing and treating T2D.

The investigators aim to study the clinical effect of sulforaphane on glucose tolerance in T2D patients. Sulforaphane will be given as BSE. BSE is a freeze-dried powder of an aqueous extract of broccoli sprouts that provides a consistent and stable source of sulforaphane. The investigators will use a parallel arm study design with patients receiving BSE or placebo. The randomization will be double-blind. The study will be done at one centre. Patients with BMI between 25-40 kg/m2 will be included. Another inclusion criterion is HbA1c 6-10%. Patients will be treated for 12 weeks to enable us to observe effects on HbA1c (HbA1c turn-over is 3 months).

Patients will come to a screening visit and if they give informed consent and are included they attend a second visit 2-3 weeks later.

The patients will undergo an oral glucose tolerance test (OGTT) before and after the 12-week treatment period. The reason for using OGTT rather than e.g. insulin clamps as the readout is that it is a harmless standard procedure that gives an integrated view of glucose tolerance.

Study Timeline

• Study Start: 2015-09
• Study First Submitted: 2016-06-12
• Study First Submitted QC: 2016-06-14
• Study First Posted: 2016-06-15
• Primary Completion: 2020-06
• Study Completion: 2020-06
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-14
• Last Update Posted: 2022-01-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

Inclusion Criteria

• Classified as type 2 diabetes
• Written informed consent
• Age: for men and women 35-75 years; for women below 75 years should be postmenopausal (defined as no menstrual bleeding since at least one year).
• Body mass index 25-40 kg/m2
• At screening visit : HbA1c 6-10 %, equivalent to 41-86 mmol/mol
• Currently treated with metformin or diet

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Exclusion Criteria

• Treatment with insulin, other anti-diabetic treatment given as injections or any oral anti-diabetic treatment except metformin
• Fasting blood glucose at screening > 15.0 mmol/L
• Active liver disease
• At screening or at any subsequent visit a level of aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) of more than three times the upper limit of the normal range
• Gastrointestinal ailments which may interfere with the ability to adequately absorb sulforaphane
• At screening visit creatinine > 130 µmol/L
• Coagulation disorder or current anti-coagulant therapy with warfarin, which may be affected by the BSE
• Diagnosed with a cardiovascular disease or event within 6 months prior to enrolment
• Systemic glucocorticoid treatment
• Herbal treatment, defined as food supplement (except multivitamin treatment) with herbal or vegetable extracts that may contain sulforaphane
• Allergy to broccoli
• Mental disorder making the patient unable to understand the study information
• Participation in other clinical trial which may affect the outcome of the present study
• Any other physical or psychiatric condition or treatment that in the judgment of the investigator makes it difficult to participate in the study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo containing maltodextrine but no active sulforaphane
BSE	sulforaphane	Broccoli sprout extract once daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Delta-HbA1c	12 weeks	difference in HbA1c before and after treatment

Secondary Outcome Measures

Name	Time	Method
Delta-fasting blood glucose	12 weeks	difference in fasting blood glucose before and after treatment