Effects of Sulforaphane in Patients With Prodromal to Mild Alzheimer's Disease

NCT04213391 | Unknown

• 1 other identifier: Wulab-AD sulforaphane
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

In this proposed study, the investigators will evaluate the efficacy, safety and related mechanism of sulforaphane in treatment of Alzheimer's disease (AD). The study will recruit 160 AD patients, and then these patients will be randomized to sulforaphane group or placebo group (80 patients per arm) for 24 weeks clinic trial. Clinical efficacy and safety assessment will be done at screen/baseline, 4 week, 12 week, and 24 week. The specific aims are to compare sulforaphane versus placebo on: clinical core symptoms; biological samples also will be collected, and stored to research related mechanisms. During the study period, safety index including blood and urine routine, liver and kidney function, coagulation index and clinical effect index about neuropsychological scales will be recorded.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• The Alzheimer's Disease Assessment Scale

  The Alzheimer's Disease Assessment Scale (ADAS-cog) will be performed to test the cognition of patients at the enrollment, week 12 and week 24. The score ranges from 0 to 75，and higher values represent a better outcome.

  From baseline to 24 weeks

Secondary Outcomes (5)

• Alzheimer's Disease Collaborative research group-Activities of Daily Living scores.

  From baseline to 24 weeks

• Neuropsychiatric Inventory scores

  baseline time to 24 weeks

• Mini-Mental State Examination scores

  baseline time to 24 weeks

• Montreal Cognitive Assessment scores

  baseline time to 24 weeks

• Clinician Interview-Based Impression of Change plus caregiver input

  baseline time to 24 weeks

Other Outcomes (6)

• Oxidative stress indexes

  At baseline and 24 week/endpoint

• Epigenetics indicators

  At baseline and 24 week/endpoint

• Cytokines & Chemokines

  At baseline and 24 week/endpoint

Study Arms (2)

sulforaphane group

EXPERIMENTAL

The patients will take sulforaphane for 24 weeks, 2550mg once a day.

Dietary Supplement: sulforaphane

Placebo group

PLACEBO COMPARATOR

The patients will take placebo for 24 weeks, 2550mg once a day.

Dietary Supplement: Placebo

Interventions

sulforaphane DIETARY_SUPPLEMENT

Sulforaphane take 2550mg once a day.

sulforaphane group

Placebo DIETARY_SUPPLEMENT

Placebo take 2550mg once a day.

Placebo group

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age range from 50 to 75 (including 50 and 75 years old), regardless of ethnic group or gender;
• \. The subjects should be able to complete the cognitive ability measurement and other tests specified in the protocol;
• \. Meeting the criteria for likely Alzheimer's Disease （AD） dementia (2011) by National Institute of Neurological Disorders and Strokes - Alzheimer's Disease and Related Diseases Association（NINCDS-ADRDA）;
• \. Patients with mild dementia: the total score of Mini-Mental State Examination (MMSE) : ≥22 points; Clinical Dementia Rating scale （CDR）score \> or equal to 0.5 and \< or equal to1；The MMSE score provides evidence of mild disease severity and the CDR-GS score indicates that the patients have noticeable amnestic (pAD) or cognitive and functional (mAD) deficits
• \. The total score of the Hachinski Ischemic Score （HIS ）was \< 4.
• \. Hamilton depression scale (17 items) total score ≤7 points;
• \. Brain MRI shows a high likelihood of AD;
• \. Before enrollment, patients should take a stable dose of dementia drugs (donepezil 5mg) ≥8 weeks;
• \. The expected survival time is \> 1 year;
• \. Subjects should have a stable and reliable caregiver, or at least have frequent contact with the caregiver (at least 3 days per week and at least 2 hours per day), who will help patients participate in the whole study; Caregivers must accompany the subjects to the visit and assist in completing the relevant scale.

You may not qualify if:

• \. Refuse to sign the inform consent form;
• \. Other causes of dementia: known vascular, central nervous system infection ,Parkinson's disease, traumatic brain dementia, other physical and chemical factors; serious body disease , intracranial space-occupying lesions, endocrine system disease, such as thyroid disease, and a lack of vitamin B12, folic acid, or any other known causes of dementia.
• \. Central nervous system diseases (including stroke, optic neuromyelitis, Parkinson's disease, epilepsy, etc.);
• \. Obvious positive signs of nervous system examination;
• \. Psychotic patients, including schizophrenia or other disorders with bipolar disorder, major depression or delirium;
• \. Uncontrolled hypertension or hypotension during screening: systolic blood pressure ≥180（millimetres of mercury ）mmHg or \< 90mmhg, or diastolic blood pressure ≥120mmHg or \< 60mmhg;
• \. Unstable or severe diseases of the heart, lung, liver, kidney and hematopoietic system according to the judgment of the researchers;
• \. Patients with incurable visual and auditory disorders that cannot complete neuropsychological tests and scales;
• \. Female subjects who are positive in pregnancy test or breast-feeding and who cannot take effective contraceptive measures or have a birth plan;
• \. Severe allergy, non-allergic drug reaction or multi-drug allergy history;
• \. Participated in other clinical trials within 3 months before screening visit;
• \. Taking any health care products related to brain and brain improvement currently and failing to keep the promise to stop using the above products;
• \. Other conditions are unsuitable for participating in this study according to the judgement of researchers.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital,Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

Related Publications (6)

• Lee S, Choi BR, Kim J, LaFerla FM, Park JHY, Han JS, Lee KW, Kim J. Sulforaphane Upregulates the Heat Shock Protein Co-Chaperone CHIP and Clears Amyloid-beta and Tau in a Mouse Model of Alzheimer's Disease. Mol Nutr Food Res. 2018 Jun;62(12):e1800240. doi: 10.1002/mnfr.201800240. Epub 2018 May 28.

  PMID: 29714053 BACKGROUND

• Hou TT, Yang HY, Wang W, Wu QQ, Tian YR, Jia JP. Sulforaphane Inhibits the Generation of Amyloid-beta Oligomer and Promotes Spatial Learning and Memory in Alzheimer's Disease (PS1V97L) Transgenic Mice. J Alzheimers Dis. 2018;62(4):1803-1813. doi: 10.3233/JAD-171110.

  PMID: 29614663 BACKGROUND

• Jhang KA, Park JS, Kim HS, Chong YH. Sulforaphane rescues amyloid-beta peptide-mediated decrease in MerTK expression through its anti-inflammatory effect in human THP-1 macrophages. J Neuroinflammation. 2018 Mar 12;15(1):75. doi: 10.1186/s12974-018-1112-x.

  PMID: 29530050 BACKGROUND

• Kim J, Lee S, Choi BR, Yang H, Hwang Y, Park JH, LaFerla FM, Han JS, Lee KW, Kim J. Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways. Mol Nutr Food Res. 2017 Feb;61(2). doi: 10.1002/mnfr.201600194. Epub 2016 Nov 30.

  PMID: 27735126 BACKGROUND

• Zhao F, Zhang J, Chang N. Epigenetic modification of Nrf2 by sulforaphane increases the antioxidative and anti-inflammatory capacity in a cellular model of Alzheimer's disease. Eur J Pharmacol. 2018 Apr 5;824:1-10. doi: 10.1016/j.ejphar.2018.01.046. Epub 2018 Jan 31.

  PMID: 29382536 BACKGROUND

• Zhang R, Zhang J, Fang L, Li X, Zhao Y, Shi W, An L. Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer's disease-like lesions. Int J Mol Sci. 2014 Aug 18;15(8):14396-410. doi: 10.3390/ijms150814396.

  PMID: 25196440 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

sulforaphane

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Qing-Qing tao, Ph.D

CONTACT

+08613777820430; qingqingtao@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: December 30, 2019
• Study Start: May 10, 2020
• Primary Completion: November 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 12, 2020

Record last verified: 2019-05

Locations

CN (1)