- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04848792
Treatment Strategy to Enhance Nrf2 Signaling in Older Adults
May 25, 2023 updated by: Northern Arizona University
Treatment Strategy to Enhance Nrf2 Signaling in Older Adults: Combining Acute Exercise With the Phytochemical Sulforaphane
Exercise is the cornerstone of disease prevention and often an important component of treatment.
However, the efficacy of an exercise stimulus is reduced with aging.
This study will investigate whether adding a treatment with phytonutrients found in cruciferous vegetables can improve the exercise response in older individuals.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
Redox balance plays a key role in the age-associated increased risk for diseases.
One reason for the lower resistance to oxidative stress with age is a gradual shift in the redox state toward a more oxidized cellular environment resulting in disruption of cell signaling.
Nuclear erythroid factor 2-related factor 2 (Nrf2) is the master regulator of antioxidant defenses.
Nrf2 drives expression of a host of genes involved in cytoprotection and antioxidant defenses.
The Traustadottir lab was the first to demonstrate Nrf2 activation in response to acute exercise in humans, and in agreement with animal data, found an age-related impairment in exercise-induced Nrf2 signaling.
This underscores an important problem related to aging, namely that older individuals are less sensitive to an exercise stimulus compared to younger cohorts.
The focus of the proposed study is to try to solve this problem by amplifying the signal and mitigating the "exercise desensitization" exhibited by older individuals to restore redox balance.
This study will test the hypothesis that combining acute exercise with sulforaphane will improve Nrf2 activation and downstream signaling in older adults compared to either alone.
Sulforaphane (SFN) is a phytonutrient found in high concentrations in cruciferous vegetables and a potent Nrf2 activator.
The hypothesis will be tested using two different approaches; the first experiment will use an in vivo-ex vivo approach, where peripheral blood mononuclear cells (PBMCs) collected from older men and women (≥60y, n=30) pre- and post-acute exercise (in vivo) will be cultured and stimulated with SFN (ex vivo).
This allows for a greater experimental control of the SFN stimulus.
The second experiment will test the clinical translation applying the sulforaphane stimulus in vivo through an oral supplementation of sulforaphane in the form of whole broccoli sprout material, prior to acute exercise, in the same individuals.
This second experiment will be a randomized placebo-controlled cross-over design.
For all trials Nrf2 signaling will be measured by Nrf2 activation through an ARE binding assay, nuclear to whole cell ratio of Nrf2 protein, and Nrf2-dependent gene expression (HO-1, GCLC, NQO1, GR).
Potential sex differences will be investigated.
The insights gained from this study are whether combining simple interventions in the category of healthy lifestyle and preventive medicine can improve the adaptive response to exercise in older individuals.
This could have an enormous impact by improving the health and well-being of older Americans.
Study Type
Interventional
Enrollment (Estimated)
30
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Tinna Traustadóttir, PhD
- Phone Number: 9285237291
- Email: tinna.traustadottir@nau.edu
Study Locations
-
-
Arizona
-
Flagstaff, Arizona, United States, 86011
- Recruiting
- Northern Arizona University
-
Contact:
- Tinna Traustadóttir, PhD
- Phone Number: 928-523-7291
- Email: tinna.traustadottir@nau.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
60 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Men and women, 60 years and older
- Competent to independently give informed consent
- Successful completion of screening
- Maximal oxygen consumption below the 60th percentile based on gender:
- Women: ≤ 21.2 mL/kg/min
- Men: ≤ 30.5 mL/kg/min
Exclusion Criteria:
- Estrogen supplementation (in any form) within the previous 6 months
- Any medication that could affect outcome measures such as statins, blood pressure medications, or anti-depressives
- Use of anti-oxidant supplements, in excess of standard multi-vitamins (1 tablet/day) and/or any supplements known to target Nrf2 including resveratrol, Protandim, and sulforaphane
- Current smoker
- Body Mass Index (BMI) greater than 33 kg/m2 (Class I Obesity)
- Any chronic illness that could affect outcome measures, including diabetes, liver or renal disease, or cancer (other than skin cancer)
- History of a myocardial infarction within the last 6 months, clinically significant aortic stenosis, use of cardiac defibrillator, or uncontrolled angina
- Clinically significant arrhythmia on a resting EKG or significant EKG changes during the baseline VO2 max test
- Any other condition that would contraindicate maximal exercise testing, including elevated blood pressure at rest (systolic BP >150 or diastolic BP >90 mm Hg on at least 2 measurements, at least 10 minutes apart) or musculoskeletal problems
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SFN supplement
The oral sulforaphane supplement is a myrosinase-active whole broccoli sprout material (EnduraCell Bioactive, Cell-Logic, Queensland, AU) containing 14 mg SFN per capsule.
Three capsules will be consumed 90 min prior to the start of the acute exercise trial.
The dose of 3 capsules is equivalent to approximately 220 µmol of SFN, which is comparable to that of other studies using broccoli sprout extracts and the recommended single dose.
|
Placebo capsules
Myrosinase-active whole broccoli sprout material
Other Names:
|
Placebo Comparator: Placebo
Placebo capsules provided by Cell-Logic.
|
Placebo capsules
Myrosinase-active whole broccoli sprout material
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Nrf2 activation in response to acute exercise
Time Frame: Comparing trials separated by one week (supplement vs. placebo)
|
Nrf2/ARE Binding Assay
|
Comparing trials separated by one week (supplement vs. placebo)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
NQO1 gene expression in response to acute exercise
Time Frame: Comparing trials separated by one week (supplement vs. placebo)
|
NQO1 mRNA measured with RT-qPCR
|
Comparing trials separated by one week (supplement vs. placebo)
|
HO-1 gene expression in response to acute exercise
Time Frame: Comparing trials separated by one week (supplement vs. placebo)
|
HO-1 mRNA measured with RT-qPCR
|
Comparing trials separated by one week (supplement vs. placebo)
|
Glutathione reductase (GR) gene expression in response to acute exercise
Time Frame: Comparing trials separated by one week (supplement vs. placebo)
|
GR mRNA measured with RT-qPCR
|
Comparing trials separated by one week (supplement vs. placebo)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 9, 2023
Primary Completion (Estimated)
June 30, 2024
Study Completion (Estimated)
June 30, 2024
Study Registration Dates
First Submitted
March 16, 2021
First Submitted That Met QC Criteria
April 16, 2021
First Posted (Actual)
April 19, 2021
Study Record Updates
Last Update Posted (Actual)
May 30, 2023
Last Update Submitted That Met QC Criteria
May 25, 2023
Last Verified
May 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1551363
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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