Colorectal Cancer Stage IVCANEX-2NCT04715061
Impact of Aerobic Exercise on Immune Response and Side Effects of Cancer Treatments
A study testing Moderate Intensity Continuous Exercise (MICE) and High Intensity Interval Exercise (HIIE) in people with Colorectal Cancer Stage IV, run by Université de Sherbrooke at 1 site in Canada.
Trial summary
Aerobic exercise is associated with many benefits in patients with cancer treatments. Among these, the reduction of cancer-related fatigue (CRF) is one of the best demonstrated. Besides, several animal models have shown a marked reduction in tumor growth with aerobic exercise, sometimes by more than 60%. Read more about this study
- Who is it for?
- Ages 50 to 65 years
- Conditions the study is for
- Colorectal Cancer Stage IV
- What is being tested?
- Moderate Intensity Continuous Exercise (MICE) and High Intensity Interval Exercise (HIIE)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteCanada
- Study dates
- 4 Nov 2020to 4 Oct 2022
- 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 50 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of metastatic colorectal cancer
- At the beginning of their chemotherapy treatment
- Eastern Cooperative Oncology Group (ECOG) performance status between grades 0 to 1
- Physically capable to realise HIIT and continous moderate aerobic exercise on ergocycle
Who cannot join
- Orthopedic, cardiac or metabolic limitations preventing aerobic effort
- Betablockers
- Surgery planned for the next two months following recruitment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Modulation of Immune Response and Side Effects of Cancer Treatments by Aerobic Exercise: Role of Exercise Intensity
Aerobic exercise is associated with many benefits in patients with cancer treatments. Among these, the reduction of cancer-related fatigue (CRF) is one of the best demonstrated. Besides, several animal models have shown a marked reduction in tumor growth with aerobic exercise, sometimes by more than 60%. As the level of physical activity is convincingly associated with a reduction in the risk of cancer or recurrences, this suggests that aerobic exercise may represent a central therapeutic approach during treatment, both against CRF and for its potential anti-tumor effect.
Both benefits have been suggested to be based on the immunostimulatory and anti-inflammatory effects of exercise. Indeed, systemic inflammatory activity seems to play a central role in the etiology of CRF during cancer treatments, among other things by stimulating the neuro-inflammatory activity of the central nervous system. Also, regarding the anti-tumor effect of exercise, animal models show that this benefit is partly explained by an increase in the activity of immune cells called natural killers (Natural Killer; NK) in tumor tissue and a reduction in the activity of regulatory T cells, the latter having an immunosuppressive effect. However, in humans, the results vary. While some improvement in NK cell activity has been reported in response to aerobic training in breast cancer survivors, others have seen no effect on the immune profile of patients and survivors. On the other hand, some authors report an improvement in the inflammatory profile with training, while others report little or no effect, as well as weak associations with the perception of fatigue.
Read more
Although these results seem to discredit the hypothesis of immune and inflammatory regulation of exercise in humans, these studies have all looked at the effect of several weeks of training on the inflammatory and immune profile on an empty stomach and rest. However, several results from the field of exercise immunology convincingly show that the anti-inflammatory effect, as well as the immunostimulating effect of aerobic exercise (including the anti-tumor activity of NK cells) are mainly acute and transient, ie. in the hours following the end of the effort. Furthermore, certain results suggest that in the context of chemotherapy treatments, cyclical treatment by nature, the peaks of fatigue are also acute (i.e. in the days following the treatment) and parallel to peaks of inflammatory activity.
Considering these results, it is therefore plausible to assume that the effect of aerobic exercise on suppressing tumor growth and reducing CRF results rather than the repetition of this acute response at each exercise session. In this case, the prescription of aerobic exercise preceding a session of chemotherapy could potentially represent an interesting therapeutic modality, allowing both the reduction of the CRF associated with this treatment, as well as a better response to the treatment. Besides, as this acute response seems to be highly dependent on the intensity of the effort, high-intensity interval training (HIIT) could be a particularly interesting approach in this context, because it does not require that the high intensity or long-lasting exercise. However, considering the immunosuppressive and pro-inflammatory effects of chemotherapy, the extent of the acute response to exercise may not allow this type of therapeutic use to be considered in this population. To date, no study has attempted to characterize the acute immune and inflammatory response following aerobic exercise in patients currently undergoing chemotherapy treatments.
- Conditions
- Colorectal Cancer Stage IV
- Being tested
- Resting state (Control), Moderate Intensity Continuous Exercise (MICE), High Intensity Interval Exercise (HIIE)
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Resting state (Control)Other
Participants were asking to sit on a sofa for 50 minutes.
Moderate Intensity Continuous Exercise (MICE)Other
MICE condition consisted of 50 minutes of moderate and continuous aerobic exercise on ergocycle. This includes a warm-up and cool-down period at low intensity, and a 40-minute period at moderate intensity (power output is equivalent to an effort perception from 4 to 6/10 and lactate levels from 2 to 4 mmol/L, obtained by submaximal test)
High Intensity Interval Exercise (HIIE)Other
HIIT condition consisted of a 30 minutes of aerobic exercise training perform on ergocycle. This includes a warm-up at low intensity, followed by 10 blocks of 1 minute at high intensity (power output corresponding to the highest power reached at the submaximal test and lactate levels > 4 mmol/L) and 1 minute of active cooldown (effort perception around 1-2/10).
| Study group | Role | What they receive |
|---|---|---|
| Cancer patients with MRI | Experimental | 9 cancer patients will be recruited and received the 3 experimental conditions : first the rest condition (with MRI), then randomly MICE condition and HIIT condition (with MRI). Receives: Other: Resting state (Control); Other: Moderate Intensity Continuous Exercise (MICE); Other: High Intensity Interval Exercise (HIIE) |
| Cancer patients without MRI | Experimental | 9 cancer patients will be recruited and received the 3 experimental conditions : first the rest condition, then randomly MICE condition and HIIT condition, all without MRI. Receives: Other: Resting state (Control); Other: Moderate Intensity Continuous Exercise (MICE); Other: High Intensity Interval Exercise (HIIE) |
| Healthy patients | Active comparator | 9 healthy patients will be recruited and received 2 experimental conditions : first the rest condition (with a MRI), then HIIT condition (with MRI). Receives: Other: Resting state (Control); Other: High Intensity Interval Exercise (HIIE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the concentration of different peripheral blood mononuclear cells (Natural Killer Cells, T cells and monocytes)
Flow cytometry
Measured: Before the start of the condition (t = 0 minute), at the end of the condition (t = 50 minutes), 1 hour post-condition (t = 110 minutes)
Secondary outcomes (6)
Change in the concentration of inflammatory mediators in peripheral blood (chemokines, pro- and anti-inflammatory cytokines)
Luminex immunoassay
Measured: Before the start of the condition (t = 0 minute), At the end of the condition (t = 50 minutes), 1 hour post-condition (t = 110 minutes), 2 hour post-condition (t = 170 minutes)
Change of hormonal profile (cortisol, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), adrenaline and noradrenaline)
ELISA Kits and Salivary Cortisol Enzyme ImmunoAssay Kit
Measured: Before the start of the condition (t = 0 minute), At the end of the condition (t = 50 minutes), 1 hour post-condition (t = 110 minutes), 2 hour post-condition (t = 170 minutes)
Change of Indoleamine-2,3-Dioxygenase activation
Liquid chromatography-mass spectrometry (LCMS)
Measured: Before the start of the condition (t = 0 minute), At the end of the condition (t = 50 minutes), 1 hour post-condition (t = 110 minutes), 2 hour post-condition (t = 170 minutes)
Cancer-Related Fatigue
Visual Analogue Scale, graduated from 0 (no fatigue) to 10 (extreme fatigue)
Measured: During 5 days after the day of the condition, 3 times per day
Cerebral integrity - Cerebral blood flow
Functional MRI (pcASL technique)
Measured: At the end of the condition (t = 50 minutes) within a 30-minute time window
Heart rate variability
Heart rate monitor
Measured: At the end of the condition, during 10 minutes (t = 50 minutes to t = 60 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2021
- Study start4 Nov 2020
- Primary completion29 Sep 2022
- Study completion4 Oct 2022
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 Colorectal Cancer Stage IVStudies of the same condition, open and under way.
- More trials run by Université de SherbrookeThe sponsor's other registered studies.
- 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Each participant performed 3 experimental conditions (rest, moderate continuous training and interval training).
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04715061
- Sponsor's protocol ID
- 2020-3547
- Acronym
- CANEX-2
- Status last verified
- Nov 2022
- First submitted
- 11 Dec 2020
- Last updated
- 7 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Parent-Roberge H, Fontvieille A, Poirier L, Tai L, Pavic M, Fulop T, Riesco E. The acute response of cytotoxic T cells following work-matched continuous moderate-intensity and high-intensity interval exercise in metastatic cancer patients undergoing chemotherapy: a pilot study. Appl Physiol Nutr Metab. 2026 Jan 1;51:1-15. doi: 10.1139/apnm-2025-0157.
PubMed 42647954
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Immune Response and Side Effects of Cancer Treatments by Aerobic Exercise: Role of Exercise Intensity
- ClinicalTrials.gov ID
- NCT04715061
- Acronym / sponsor ID
- CANEX-2 / 2020-3547
- Conditions
- Colorectal Cancer Stage IV
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Université de SherbrookeUniversity, hospital or other
- Study start
- 4 Nov 2020 (actual)
- Primary completion
- 29 Sep 2022 (actual)
- Study completion
- 4 Oct 2022 (actual)
- First posted
- 20 Jan 2021 (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.
Aerobic exercise is associated with many benefits in patients with cancer treatments. Among these, the reduction of cancer-related fatigue (CRF) is one of the best demonstrated. Besides, several animal models have shown a marked reduction in tumor growth with aerobic exercise, sometimes by more than 60%. As the level of physical activity is convincingly associated with a reduction in the risk of cancer or recurrences, this suggests that aerobic exercise may represent a central therapeutic approach during treatment, both against CRF and for its potential anti-tumor effect.
Both benefits have been suggested to be based on the immunostimulatory and anti-inflammatory effects of exercise. Indeed, systemic inflammatory activity seems to play a central role in the etiology of CRF during cancer treatments, among other things by stimulating the neuro-inflammatory activity of the central nervous system. Also, regarding the anti-tumor effect of exercise, animal models show that this benefit is partly explained by an increase in the activity of immune cells called natural killers (Natural Killer; NK) in tumor tissue and a reduction in the activity of regulatory T cells, the latter having an immunosuppressive effect. However, in humans, the results vary. While some improvement in NK cell activity has been reported in response to aerobic training in breast cancer survivors, others have seen no effect on the immune profile of patients and survivors. On the other hand, some authors report an improvement in the inflammatory profile with training, while others report little or no effect, as well as weak associations with the perception of fatigue.
Although these results seem to discredit the hypothesis of immune and inflammatory regulation of exercise in humans, these studies have all looked at the effect of several weeks of training on the inflammatory and immune profile on an empty stomach and rest. However, several results from the field of exercise immunology convincingly show that the anti-inflammatory effect, as well as the immunostimulating effect of aerobic exercise (including the anti-tumor activity of NK cells) are mainly acute and transient, ie. in the hours following the end of the effort. Furthermore, certain results suggest that in the context of chemotherapy treatments, cyclical treatment by nature, the peaks of fatigue are also acute (i.e. in the days following the treatment) and parallel to peaks of inflammatory activity.
Considering these results, it is therefore plausible to assume that the effect of aerobic exercise on suppressing tumor growth and reducing CRF results rather than the repetition of this acute response at each exercise session. In this case, the prescription of aerobic exercise preceding a session of chemotherapy could potentially represent an interesting therapeutic modality, allowing both the reduction of the CRF associated with this treatment, as well as a better response to the treatment. Besides, as this acute response seems to be highly dependent on the intensity of the effort, high-intensity interval training (HIIT) could be a particularly interesting approach in this context, because it does not require that the high intensity or long-lasting exercise. However, considering the immunosuppressive and pro-inflammatory effects of chemotherapy, the extent of the acute response to exercise may not allow this type of therapeutic use to be considered in this population. To date, no study has attempted to characterize the acute immune and inflammatory response following aerobic exercise in patients currently undergoing chemotherapy treatments.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Each participant performed 3 experimental conditions (rest, moderate continuous training and interval training).
| Arm | Type | Receives |
|---|---|---|
| Cancer patients with MRI | Experimental | Other: Resting state (Control), Other: Moderate Intensity Continuous Exercise (MICE), Other: High Intensity Interval Exercise (HIIE)9 cancer patients will be recruited and received the 3 experimental conditions : first the rest condition (with MRI), then randomly MICE condition and HIIT condition (with MRI). |
| Cancer patients without MRI | Experimental | Other: Resting state (Control), Other: Moderate Intensity Continuous Exercise (MICE), Other: High Intensity Interval Exercise (HIIE)9 cancer patients will be recruited and received the 3 experimental conditions : first the rest condition, then randomly MICE condition and HIIT condition, all without MRI. |
| Healthy patients | Active comparator | Other: Resting state (Control), Other: High Intensity Interval Exercise (HIIE)9 healthy patients will be recruited and received 2 experimental conditions : first the rest condition (with a MRI), then HIIT condition (with MRI). |
Who may qualify
- Ages
- 50 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of metastatic colorectal cancer
- At the beginning of their chemotherapy treatment
- Eastern Cooperative Oncology Group (ECOG) performance status between grades 0 to 1
- Physically capable to realise HIIT and continous moderate aerobic exercise on ergocycle
Key exclusion criteria (3 listed)
- Orthopedic, cardiac or metabolic limitations preventing aerobic effort
- Betablockers
- Surgery planned for the next two months following recruitment
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 |
|---|---|---|
| Resting state (Control)Participants were asking to sit on a sofa for 50 minutes. | Other | Cancer patients with MRI, Cancer patients without MRI, Healthy patients |
| Moderate Intensity Continuous Exercise (MICE)MICE condition consisted of 50 minutes of moderate and continuous aerobic exercise on ergocycle. This includes a warm-up and cool-down period at low intensity, and a 40-minute period at moderate intensity (power output is equivalent to an effort perception from 4 to 6/10 and lactate levels from 2 to 4 mmol/L, obtained by submaximal test) | Other | Cancer patients with MRI, Cancer patients without MRI |
| High Intensity Interval Exercise (HIIE)HIIT condition consisted of a 30 minutes of aerobic exercise training perform on ergocycle. This includes a warm-up at low intensity, followed by 10 blocks of 1 minute at high intensity (power output corresponding to the highest power reached at the submaximal test and lactate levels > 4 mmol/L) and 1 minute of active cooldown (effort perception around 1-2/10). | Other | Cancer patients with MRI, Cancer patients without MRI, Healthy patients |
Primary outcome
Change in the concentration of different peripheral blood mononuclear cells (Natural Killer Cells, T cells and monocytes)
Time frame: Before the start of the condition (t = 0 minute), at the end of the condition (t = 50 minutes), 1 hour post-condition (t = 110 minutes)
Flow cytometry
6 secondary outcomes
Change in the concentration of inflammatory mediators in peripheral blood (chemokines, pro- and anti-inflammatory cytokines)
Time frame: Before the start of the condition (t = 0 minute), At the end of the condition (t = 50 minutes), 1 hour post-condition (t = 110 minutes), 2 hour post-condition (t = 170 minutes)
Change of hormonal profile (cortisol, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), adrenaline and noradrenaline)
Time frame: Before the start of the condition (t = 0 minute), At the end of the condition (t = 50 minutes), 1 hour post-condition (t = 110 minutes), 2 hour post-condition (t = 170 minutes)
Change of Indoleamine-2,3-Dioxygenase activation
Time frame: Before the start of the condition (t = 0 minute), At the end of the condition (t = 50 minutes), 1 hour post-condition (t = 110 minutes), 2 hour post-condition (t = 170 minutes)
Cancer-Related Fatigue
Time frame: During 5 days after the day of the condition, 3 times per day
Cerebral integrity - Cerebral blood flow
Time frame: At the end of the condition (t = 50 minutes) within a 30-minute time window
Heart rate variability
Time frame: At the end of the condition, during 10 minutes (t = 50 minutes to t = 60 minutes)
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 7 Nov 2022.
- Derived from this study: PubMed 42647954Parent-Roberge H, Fontvieille A, Poirier L, Tai L, Pavic M, Fulop T, Riesco E. The acute response of cytotoxic T cells following work-matched continuous moderate-intensity and high-intensity interval exercise in metastatic cancer patients undergoing chemotherapy: a pilot study. Appl Physiol Nutr Metab. 2026 Jan 1;51:1-15. doi: 10.1139/apnm-2025-0157.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Moderate Intensity Continuous Exercise (MICE) and High Intensity Interval Exercise (HIIE) in people with Colorectal Cancer Stage IV, run by Université de Sherbrooke at 1 site in Canada.
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 4 inclusion and 3 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 7 Nov 2022. 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 Canada. 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?
Change in the concentration of different peripheral blood mononuclear cells (Natural Killer Cells, T cells and monocytes) (time frame: Before the start of the condition (t = 0 minute), at the end of the condition (t = 50 minutes), 1 hour post-condition (t = 110 minutes)). 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 NCT04715061, 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 7 Nov 2022.