AgingNCT03419988
Cell Signaling and Resistance to Oxidative Stress: Effects of Aging and Exercise
A study testing Exercise Intervention in people with Aging, run by Northern Arizona University at 1 site in United States.
Trial summary
Advanced age is the main risk factor for chronic diseases such as cardiovascular disease, type 2 diabetes, Alzheimer's disease and cancer. One reason may be due to decreased resistance to oxidative stress as antioxidant defenses and cell protection is reduced with aging. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Exercise Intervention
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2017to 30 Jun 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women, 18-28 years or 60 years and older
- Competent to independently give informed consent
- Successful completion of screening
- No regular exercise for the past 6-months (by self-report)
- A score below 3.0 on the Historical Lifetime Physical Activity Questionnaire
Who cannot join
- Estrogen supplementation within the previous 6 months
- Use of anti-oxidant supplements, in excess of standard multi-vitamins (1 tablet/day)
- Current smoker
- Body Mass Index (BMI) ≤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 maximal oxygen consumption (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
Trial locations and contacts
1 site in 1 country.
United States1 site
Northern Arizona University
Flagstaff, Arizona, 86011
About this study
Advanced age is the main risk factor for chronic diseases such as cardiovascular disease, type 2 diabetes, Alzheimer's disease and cancer. One reason may be due to decreased resistance to oxidative stress as antioxidant defenses and cell protection is reduced with aging. This has been shown in animal studies and also that the impairment can be somewhat restored with exercise. This will be the first study to test this in humans by comparing young and older inactive adults before and after an exercise intervention, a practical and cost-effective intervention that can have tremendous public health impact by lowering risk for disease and medical-related costs.
Read the detailed description
Advanced age substantially increases the risk for a host of diseases including cardiovascular disease, type 2 diabetes, Alzheimer's disease, and cancer. A major factor that appears to underlie this increased risk with age is reduced capacity to resist oxidative injury or oxidative stress. Therefore, maintaining or increasing the capacity to resist oxidative stress appears critical to the prevention of age-related disease and promotion of successful aging. One potential reason for the lower resistance to oxidative stress with age is a gradual shift in the redox state toward a more oxidized cellular environment potentially disrupting cell-signaling. Nuclear erythroid-2-p45-related factor-2 (Nrf2) is the master regulator of antioxidant defenses. Nrf2 drives expression of a host of genes involved in cellular detoxification and antioxidant defenses. There is strong evidence from animal studies that Nrf2 signaling is reduced with aging and can be at least partially restored with moderate exercise training, however the gap in current knowledge is whether these data do in fact translate to humans. This study will test the following hypotheses in young and older men and women: i) aging is associated with impaired Nrf2 signaling in response to acute exercise and ii) moderate exercise training will improve Nrf2 signaling in older, inactive individuals, and this will increase their resistance to oxidative stress. These hypotheses will be tested by comparing 25 young (18-28y) and 25 older (≥60y) inactive individuals before and after an 8-week exercise intervention (n=15 per age group) and in comparison to non-exercising age-matched control groups (n=10 per age group). Nrf2 signaling will be measured in peripheral blood mononuclear cells (PBMCs) in response to acute exercise and will include gene expression (NRF2, NQO1, HO1, GCLC), protein abundance (NRF2, KEAP1, NQO1, HO1, GCLC) and Nrf2-ARE binding capacity. Resistance to oxidative stress will be measured by plasma F2-isoprostane response to forearm ischemia/reperfusion. The results will increase understanding of the mechanisms of diminished stress resilience with aging and the plasticity of these pathways. This will determine whether targeting Nrf2 signaling will be effective for prevention or treatment of these age-related changes which has an enormous public health impact due to the potential of lowering disease risk and medical costs. An additional significance of this project is creating opportunity for undergraduate and graduate students to become involved in research, an important purpose of the Academic Research Enhancement Award (AREA) program and a mission of Northern Arizona University.
- Conditions
- Aging
- Being tested
- Exercise Intervention
- Keywords
- Nrf2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise InterventionBehavioural
24 sessions of aerobic exercise
| Study group | Role | What they receive |
|---|---|---|
| Exercise Intervention | Experimental | 8-weeks exercise intervention: 3-days per week for 45-55 minutes per session Receives: Behavioral: Exercise Intervention |
| Control | No intervention | 8-weeks control: asked not to change anything or start exercising. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cell signaling
Nuclear Nrf2 protein content in peripheral mononuclear cells (PBMCs) in response to acute exercise
Measured: 8 weeks
Resistance to oxidative stress
F2-isoprostane response to forearm ischemia-reperfusion
Measured: 8 weeks
Secondary outcomes (1)
Cell signaling
GCLC protein abundance in PBMCs in response to acute exercise
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start1 Jun 2017
- Primary completion30 May 2020
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized control trial: exercise intervention versus non-exercise control
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northern Arizona University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tinna Traustadottir, Northern Arizona University
- Investigators
- Tinna Traustadóttir, PhD, Principal investigator, Northern Arizona University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03419988
- Sponsor's protocol ID
- R15AG055077
- Status last verified
- Aug 2020
- First submitted
- 11 Jan 2018
- Last updated
- 26 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ostrom EL, Traustadottir T. Aerobic exercise training partially reverses the impairment of Nrf2 activation in older humans. Free Radic Biol Med. 2020 Nov 20;160:418-432. doi: 10.1016/j.freeradbiomed.2020.08.016. Epub 2020 Aug 28.
PubMed 32866619
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cell Signaling and Resistance to Oxidative Stress: Effects of Aging and Exercise
- ClinicalTrials.gov ID
- NCT03419988
- Acronym / sponsor ID
- R15AG055077
- Conditions
- Aging
- Keywords
- Nrf2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Northern Arizona UniversityUniversity, hospital or other
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 30 May 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 5 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Advanced age is the main risk factor for chronic diseases such as cardiovascular disease, type 2 diabetes, Alzheimer's disease and cancer. One reason may be due to decreased resistance to oxidative stress as antioxidant defenses and cell protection is reduced with aging. This has been shown in animal studies and also that the impairment can be somewhat restored with exercise. This will be the first study to test this in humans by comparing young and older inactive adults before and after an exercise intervention, a practical and cost-effective intervention that can have tremendous public health impact by lowering risk for disease and medical-related costs.
Detailed description
Advanced age substantially increases the risk for a host of diseases including cardiovascular disease, type 2 diabetes, Alzheimer's disease, and cancer. A major factor that appears to underlie this increased risk with age is reduced capacity to resist oxidative injury or oxidative stress. Therefore, maintaining or increasing the capacity to resist oxidative stress appears critical to the prevention of age-related disease and promotion of successful aging. One potential reason for the lower resistance to oxidative stress with age is a gradual shift in the redox state toward a more oxidized cellular environment potentially disrupting cell-signaling. Nuclear erythroid-2-p45-related factor-2 (Nrf2) is the master regulator of antioxidant defenses. Nrf2 drives expression of a host of genes involved in cellular detoxification and antioxidant defenses. There is strong evidence from animal studies that Nrf2 signaling is reduced with aging and can be at least partially restored with moderate exercise training, however the gap in current knowledge is whether these data do in fact translate to humans. This study will test the following hypotheses in young and older men and women: i) aging is associated with impaired Nrf2 signaling in response to acute exercise and ii) moderate exercise training will improve Nrf2 signaling in older, inactive individuals, and this will increase their resistance to oxidative stress. These hypotheses will be tested by comparing 25 young (18-28y) and 25 older (≥60y) inactive individuals before and after an 8-week exercise intervention (n=15 per age group) and in comparison to non-exercising age-matched control groups (n=10 per age group). Nrf2 signaling will be measured in peripheral blood mononuclear cells (PBMCs) in response to acute exercise and will include gene expression (NRF2, NQO1, HO1, GCLC), protein abundance (NRF2, KEAP1, NQO1, HO1, GCLC) and Nrf2-ARE binding capacity. Resistance to oxidative stress will be measured by plasma F2-isoprostane response to forearm ischemia/reperfusion. The results will increase understanding of the mechanisms of diminished stress resilience with aging and the plasticity of these pathways. This will determine whether targeting Nrf2 signaling will be effective for prevention or treatment of these age-related changes which has an enormous public health impact due to the potential of lowering disease risk and medical costs. An additional significance of this project is creating opportunity for undergraduate and graduate students to become involved in research, an important purpose of the Academic Research Enhancement Award (AREA) program and a mission of Northern Arizona University.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized control trial: exercise intervention versus non-exercise control
| Arm | Type | Receives |
|---|---|---|
| Exercise Intervention | Experimental | Behavioral: Exercise Intervention8-weeks exercise intervention: 3-days per week for 45-55 minutes per session |
| Control | No intervention | –8-weeks control: asked not to change anything or start exercising. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and women, 18-28 years or 60 years and older
- Competent to independently give informed consent
- Successful completion of screening
- No regular exercise for the past 6-months (by self-report)
- A score below 3.0 on the Historical Lifetime Physical Activity Questionnaire
Key exclusion criteria (8 listed)
- Estrogen supplementation within the previous 6 months
- Use of anti-oxidant supplements, in excess of standard multi-vitamins (1 tablet/day)
- Current smoker
- Body Mass Index (BMI) ≤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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise Intervention24 sessions of aerobic exercise | Behavioural | Exercise Intervention |
Primary outcome
Cell signaling
Time frame: 8 weeks
Nuclear Nrf2 protein content in peripheral mononuclear cells (PBMCs) in response to acute exercise
Resistance to oxidative stress
Time frame: 8 weeks
F2-isoprostane response to forearm ischemia-reperfusion
1 secondary outcome
Cell signaling
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2020.
- Derived from this study: PubMed 32866619Ostrom EL, Traustadottir T. Aerobic exercise training partially reverses the impairment of Nrf2 activation in older humans. Free Radic Biol Med. 2020 Nov 20;160:418-432. doi: 10.1016/j.freeradbiomed.2020.08.016. Epub 2020 Aug 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tinna Traustadóttir, PhD principal investigator
Northern Arizona University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise Intervention in people with Aging, run by Northern Arizona University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cell signaling (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03419988, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2020.