Long-term Effects Secondary to Cancer Therapy in AdultsPhase 3NCT02468882
Does Watercress Intake Have an Impact on Cancer Patients Outcomes: a Longitudinal Trial
A Phase 3 study testing Watercress in people with Long-term Effects Secondary to Cancer Therapy in Adults, run by University of Lisbon at 1 site in Portugal.
Trial summary
Population studies associate a higher intake of cruciferous vegetables with a reduced risk of cancer. Studies identified PEITC and several active isothiocyanates in watercress extract that may have significant anticarcinogenic activity. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Long-term Effects Secondary to Cancer Therapy in Adults
- What is being tested?
- Watercress
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 sitePortugal
- Study dates
- Mar 2014to Jan 2019
- Phase
- Phase 3
- 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 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- adult breast cancer female patients consecutively referred for primary radiotherapy with curative intent
Who cannot join
- pregnancy
- cognitive impairment
- uncooperative or
- patients with any implantable electronic device (e.g. pacemaker) or internal metal material preventing BIA phase angle assessment
Trial locations and contacts
1 site in 1 country.
Paula Ravasco, MD PhD contact
Portugal1 site, 1 recruiting
- Recruiting
Hospital de Santa Maria
Lisbon
Paula Ravasco, PhD, p.ravasco@medicina.ulisboa.pt
About this study
Official title: Does Watercress Intake Have an Impact on Cancer Patients Outcomes: a Randomized Longitudinal Trial
Population studies associate a higher intake of cruciferous vegetables with a reduced risk of cancer. Studies identified PEITC and several active isothiocyanates in watercress extract that may have significant anticarcinogenic activity. Potential anticarcinogenic mechanisms include: preventing carcinogen activation by inhibiting phase I enzymes such as cytochrome P450s, by increasing cells' resistance through detoxification/antioxidant enzymes, by inhibiting cell cycle progression and/or by inducing apoptosis.
These findings are justifiably interesting for the primary care setting and cancer primary prevention. Yet, these cellular effects of watercress supplementation may further prove useful in the modulation of cancer progression and disease recurrence. The present clinical trial of nutritional supplementation in cancer, intends to further explore the effects of therapeutic diets supplemented with nutraceuticals via watercress that may prove useful in DNA damage modulation, as well as in the global disease prognosis.
Read the detailed description
The relation between cancer and nutrition has been well established; cancer builds upon damage to cellular DNA resulting from carcinogenic environmental factors, in which nutrition plays a major role. Many diet and lifestyle factors can influence the development of cancer, a disease expected to affect worldwide more than 1 in 3 people. Population studies associate a higher intake of cruciferous vegetables with a reduced risk of cancers at several locations. In 1977, a study in laboratory animals showed the potential effect of phenylethyl isothiocyanate (PEITC) to inhibit carcinogenesis. Recent studies identified several active isothiocyanates in watercress extract that may have more significant anticarcinogenic activity than PEITC alone. Potential anticarcinogenic mechanisms include: preventing carcinogen activation by inhibiting phase I enzymes such as cytochrome P450s, by increasing cells' resistance through detoxification/antioxidant enzymes; e.g. phase II enzymes (quinone reductase, glutathione S-transferases, UDP glucuronosyltransferases);, by inhibiting cell cycle progression and/or by inducing apoptosis.
Several watercress components have antigenotoxic effects in vitro resulting in reduced DNA damage and have anti-proliferative effects. These components include flavonols such as quercetin, hydroxycinnamic acids such as ferulic acid and p-coumaric acid. In HT29 colon cancer cells, an extract of watercress juice was associated with inhibition of the three stages of carcinogenesis: initiation, proliferation and metastasis. In MDA-MB-23 human breast cancer cells, watercress extract inhibited metalloproteinase-9 activity, thus suppressing the invasive potential of cancer cells. In breast cancer, epidemiological studies suggest that cruciferous vegetables may reduce cancer incidence. In animal studies, a 9-week PEITC-NAC supplemented diet vs a non-supplemented diet was significantly associated with reduction in tumour size and weight.
A recognised mechanism by which PEITC inhibits the growth and survival of established cancer cells is through the inhibition of angiogenesis. A study explored the impact of PEITC on a specific pathway central to angiogenesis by exposing human MCF7 breast cancer cells to PEITC and measuring hypoxia inducible factor (HIF) signaling activity. PEITC was shown as an effective inhibitor of HIF activity which may contribute to its anti-angiogenic and anti-cancer properties. A follow up to this experiment demonstrated that, similar to PEITC, crude watercress extracts inhibited cancer cell growth and HIF activity in vitro. Furthermore 6 to 8 hours after a significant amount dietary intake of watercress by four healthy participants, peripheral blood cells demonstrated significantly reduced HIF signalling activity, suggesting that dietary intake of watercress may be sufficient to modulate this potential anti-cancer pathway.
Of further relevance, a blind, randomized crossover study was carried out in 60 healthy volunteers instructed to consume one pack (85g) of raw watercress daily for 8 weeks. Compared to the control phase, watercress supplementation increased lymphocytes' DNA resistance to free radicals, thus reducing DNA damage. The hypothesis set out was that watercress may reduce cancer risk via decreased damage to DNA and possible effects on antioxidant status by increasing levels of plasma carotenoids.
These findings are justifiably interesting for the primary care setting and cancer primary prevention. Yet, these cellular effects of watercress supplementation may further prove useful in the modulation of cancer progression and disease recurrence, a not yet explored area. Of note, that the role of nutrition intervention in medium and long term outcomes in cancer has been demonstrated. It is today acknowledged as grade A evidence that individualized nutritional counseling and education plays a central role in improving long-term outcomes in cancer, by prolonging survival, reducing late RT toxicity and improving QoL. The present clinical trial of nutritional supplementation in cancer, intends to further explore the effects of therapeutic diets supplemented with nutraceuticals via watercress that may prove useful in DNA damage modulation, as well as in the global disease prognosis.
- Being tested
- Watercress
- Keywords
- Breast cancer, Radiotherapy, Toxicity, Outcomes, Watercress
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WatercressDietary supplement
100g of watercress daily during radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Watercress will be tested in its natural form as a food item that will supplement the usual diet, via the prescription of watercress as whole food added daily to the usual diet. The intervention group will be asked to consume 100 grams of watercress per day, in addition to their usual diet for the total time of RT treatment. These 100 grams of watercress per day will allow the achievement of the daily "therapeutic" dose. Receives: Dietary Supplement: Watercress |
| Control group | No intervention | The control group will receive the standard of care, thus will maintain their ad libitum diet. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cell phase angle
as an indirect measure of cell membrane integrity, function and metabolism
Measured: Change from baseline at up to 6 weeks
body composition
assessed by tetrapolar multifrequency Bioimpedance Analysis (BIA) and CT scan images; CT scans analysis will be performed in collaboration with expert groups
Measured: Change from baseline at up to 6 weeks
treatments' toxicity and symptoms
Assessed by the RTOG Common Toxicity Criteria, developed by the Eastern Cooperative Oncology Group (RTOG)
Measured: up to 6 weeks
RT induced skin dermitis
Evaluated by a radiation oncologist, using a validated toxicity scale
Measured: up to 6weeks
Quality of Life (QoL)
will be assessed by the European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30), validated for Oncology
Measured: Change from baseline at up to 6 weeks
DNA damage
DNA damage assessment by Comet assay in lymphocytes has been used extensively as a surrogate biomarker to measure exposure to genotoxic agents and assess cancer risk in human studies by us and others. biological samples will comprise serum or plasma (1 mL) prepared from blood samples collected in Heparin tubes and urine (1 mL). Metabolomic profiles will be measured on a 700 MHz 1H NMR spectrometer equipped with a cryo-probe for enhanced sensitivity. 1H NMR spectroscopy: high throughput metabolic phenotyping is a powerful approach for characterising biochemical signatures of biological samples. We will couple high-resolution 1H NMR spectroscopy and mathematical modelling approaches to determine the metabolic profile in biological samples from patients.
Measured: Change from baseline at up to 6 weeks
Metabolomic profile
Metabolomics simultaneously measures thousands of low molecular weight metabolites providing holistic information on the biochemical status of the body. Previous metabolomic studies have identified cancer-associated perturbations in the metabolic phenotypes of patients. This study will explore the ability of watercress to improve the restorative effects of radiotherapy in breast cancer patients on the metabolic status towards a healthy phenotype
Measured: Change from baseline at up to 6 weeks
Nutritional status
assessed by the method Patient-Generated Subjective Global Assessment, specific and validated for Oncology
Measured: Change from baseline at up to 6 weeks
Dietary intake
Will derive from a diet history and a 24-hour-recall food questionnaire. The software Dietplan6 (Forestfield Software Ltd 2013®, Horsham, UK) will analyze the nutrient content of foods consumed
Measured: Change from baseline at up to 6 weeks
Carotenoids and flavonoids
The plasma samples analysis will also include the measurement of carotenoids and flavonoids, which are present in watercress, and are related with antigenotoxic effects in vitro and have anti-proliferative effects, as demonstrated in several studies. Urine samples analysis will allow the measurement of flavonoids.
Measured: Change from baseline at up to 6 weeks
Secondary outcomes (6)
Cell phase angle 2
as an indirect measure of cell membrane integrity, function and metabolism
Measured: change from 3 months at 3 years
body composition 2
assessed by tetrapolar multifrequency Bioimpedance Analysis (BIA)
Measured: change from 3 months at 3 years
Quality of Life 2 (QoL2)
will be assessed by the European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30), validated for Oncology
Measured: change from 3 months at 3 years
Metabolomic profile 2
Metabolomics simultaneously measures thousands of low molecular weight metabolites providing holistic information on the biochemical status of the body. Previous metabolomic studies have identified cancer-associated perturbations in the metabolic phenotypes of patients. This study will explore the ability of watercress to improve the restorative effects of radiotherapy in breast cancer patients on the metabolic status towards a healthy phenotype
Measured: change from 3 months at 3 years
Nutritional status 2
assessed by the method Patient-Generated Subjective Global Assessment, specific and validated for Oncology
Measured: change from 3 months at 3 years
Dietary intake 2
Will derive from a diet history and a 24-hour-recall food questionnaire. The software Dietplan6 (Forestfield Software Ltd 2013®, Horsham, UK) will analyze the nutrient content of foods consumed
Measured: change from 3 months at 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study startMar 2014
- Primary completionJan 2019 (estimated)
- Study completionJan 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long-term Effects Secondary to Cancer Therapy in AdultsStudies 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 3
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Lisbon
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paula Ravasco, University of Lisbon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02468882
- Sponsor's protocol ID
- ULisbon
- Status last verified
- Jun 2015
- First submitted
- 21 May 2015
- Last updated
- 11 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Watercress Intake Have an Impact on Cancer Patients Outcomes: a Randomized Longitudinal Trial
- ClinicalTrials.gov ID
- NCT02468882
- Acronym / sponsor ID
- ULisbon
- Keywords
- Breast cancer, Radiotherapy, Toxicity, Outcomes, Watercress
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of LisbonUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Jan 2019 (estimated)
- First posted
- 11 Jun 2015 (estimated)
- 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.
Population studies associate a higher intake of cruciferous vegetables with a reduced risk of cancer. Studies identified PEITC and several active isothiocyanates in watercress extract that may have significant anticarcinogenic activity. Potential anticarcinogenic mechanisms include: preventing carcinogen activation by inhibiting phase I enzymes such as cytochrome P450s, by increasing cells' resistance through detoxification/antioxidant enzymes, by inhibiting cell cycle progression and/or by inducing apoptosis.
These findings are justifiably interesting for the primary care setting and cancer primary prevention. Yet, these cellular effects of watercress supplementation may further prove useful in the modulation of cancer progression and disease recurrence. The present clinical trial of nutritional supplementation in cancer, intends to further explore the effects of therapeutic diets supplemented with nutraceuticals via watercress that may prove useful in DNA damage modulation, as well as in the global disease prognosis.
Detailed description
The relation between cancer and nutrition has been well established; cancer builds upon damage to cellular DNA resulting from carcinogenic environmental factors, in which nutrition plays a major role. Many diet and lifestyle factors can influence the development of cancer, a disease expected to affect worldwide more than 1 in 3 people. Population studies associate a higher intake of cruciferous vegetables with a reduced risk of cancers at several locations. In 1977, a study in laboratory animals showed the potential effect of phenylethyl isothiocyanate (PEITC) to inhibit carcinogenesis. Recent studies identified several active isothiocyanates in watercress extract that may have more significant anticarcinogenic activity than PEITC alone. Potential anticarcinogenic mechanisms include: preventing carcinogen activation by inhibiting phase I enzymes such as cytochrome P450s, by increasing cells' resistance through detoxification/antioxidant enzymes; e.g. phase II enzymes (quinone reductase, glutathione S-transferases, UDP glucuronosyltransferases);, by inhibiting cell cycle progression and/or by inducing apoptosis.
Several watercress components have antigenotoxic effects in vitro resulting in reduced DNA damage and have anti-proliferative effects. These components include flavonols such as quercetin, hydroxycinnamic acids such as ferulic acid and p-coumaric acid. In HT29 colon cancer cells, an extract of watercress juice was associated with inhibition of the three stages of carcinogenesis: initiation, proliferation and metastasis. In MDA-MB-23 human breast cancer cells, watercress extract inhibited metalloproteinase-9 activity, thus suppressing the invasive potential of cancer cells. In breast cancer, epidemiological studies suggest that cruciferous vegetables may reduce cancer incidence. In animal studies, a 9-week PEITC-NAC supplemented diet vs a non-supplemented diet was significantly associated with reduction in tumour size and weight.
A recognised mechanism by which PEITC inhibits the growth and survival of established cancer cells is through the inhibition of angiogenesis. A study explored the impact of PEITC on a specific pathway central to angiogenesis by exposing human MCF7 breast cancer cells to PEITC and measuring hypoxia inducible factor (HIF) signaling activity. PEITC was shown as an effective inhibitor of HIF activity which may contribute to its anti-angiogenic and anti-cancer properties. A follow up to this experiment demonstrated that, similar to PEITC, crude watercress extracts inhibited cancer cell growth and HIF activity in vitro. Furthermore 6 to 8 hours after a significant amount dietary intake of watercress by four healthy participants, peripheral blood cells demonstrated significantly reduced HIF signalling activity, suggesting that dietary intake of watercress may be sufficient to modulate this potential anti-cancer pathway.
Of further relevance, a blind, randomized crossover study was carried out in 60 healthy volunteers instructed to consume one pack (85g) of raw watercress daily for 8 weeks. Compared to the control phase, watercress supplementation increased lymphocytes' DNA resistance to free radicals, thus reducing DNA damage. The hypothesis set out was that watercress may reduce cancer risk via decreased damage to DNA and possible effects on antioxidant status by increasing levels of plasma carotenoids.
These findings are justifiably interesting for the primary care setting and cancer primary prevention. Yet, these cellular effects of watercress supplementation may further prove useful in the modulation of cancer progression and disease recurrence, a not yet explored area. Of note, that the role of nutrition intervention in medium and long term outcomes in cancer has been demonstrated. It is today acknowledged as grade A evidence that individualized nutritional counseling and education plays a central role in improving long-term outcomes in cancer, by prolonging survival, reducing late RT toxicity and improving QoL. The present clinical trial of nutritional supplementation in cancer, intends to further explore the effects of therapeutic diets supplemented with nutraceuticals via watercress that may prove useful in DNA damage modulation, as well as in the global disease prognosis.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Dietary Supplement: WatercressWatercress will be tested in its natural form as a food item that will supplement the usual diet, via the prescription of watercress as whole food added daily to the usual diet. The intervention group will be asked to consume 100 grams of watercress per day, in addition to their usual diet for the total time of RT treatment. These 100 grams of watercress per day will allow the achievement of the daily "therapeutic" dose. |
| Control group | No intervention | –The control group will receive the standard of care, thus will maintain their ad libitum diet. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- adult breast cancer female patients consecutively referred for primary radiotherapy with curative intent
Key exclusion criteria (4 listed)
- pregnancy
- cognitive impairment
- uncooperative or
- patients with any implantable electronic device (e.g. pacemaker) or internal metal material preventing BIA phase angle assessment
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 |
|---|---|---|
| Watercress100g of watercress daily during radiation therapy | Dietary supplement | Intervention group |
Primary outcome
Cell phase angle
Time frame: Change from baseline at up to 6 weeks
as an indirect measure of cell membrane integrity, function and metabolism
body composition
Time frame: Change from baseline at up to 6 weeks
assessed by tetrapolar multifrequency Bioimpedance Analysis (BIA) and CT scan images; CT scans analysis will be performed in collaboration with expert groups
treatments' toxicity and symptoms
Time frame: up to 6 weeks
Assessed by the RTOG Common Toxicity Criteria, developed by the Eastern Cooperative Oncology Group (RTOG)
RT induced skin dermitis
Time frame: up to 6weeks
Evaluated by a radiation oncologist, using a validated toxicity scale
Quality of Life (QoL)
Time frame: Change from baseline at up to 6 weeks
will be assessed by the European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30), validated for Oncology
DNA damage
Time frame: Change from baseline at up to 6 weeks
DNA damage assessment by Comet assay in lymphocytes has been used extensively as a surrogate biomarker to measure exposure to genotoxic agents and assess cancer risk in human studies by us and others. biological samples will comprise serum or plasma (1 mL) prepared from blood samples collected in Heparin tubes and urine (1 mL). Metabolomic profiles will be measured on a 700 MHz 1H NMR spectrometer equipped with a cryo-probe for enhanced sensitivity. 1H NMR spectroscopy: high throughput metabolic phenotyping is a powerful approach for characterising biochemical signatures of biological samples. We will couple high-resolution 1H NMR spectroscopy and mathematical modelling approaches to determine the metabolic profile in biological samples from patients.
Metabolomic profile
Time frame: Change from baseline at up to 6 weeks
Metabolomics simultaneously measures thousands of low molecular weight metabolites providing holistic information on the biochemical status of the body. Previous metabolomic studies have identified cancer-associated perturbations in the metabolic phenotypes of patients. This study will explore the ability of watercress to improve the restorative effects of radiotherapy in breast cancer patients on the metabolic status towards a healthy phenotype
Nutritional status
Time frame: Change from baseline at up to 6 weeks
assessed by the method Patient-Generated Subjective Global Assessment, specific and validated for Oncology
Dietary intake
Time frame: Change from baseline at up to 6 weeks
Will derive from a diet history and a 24-hour-recall food questionnaire. The software Dietplan6 (Forestfield Software Ltd 2013®, Horsham, UK) will analyze the nutrient content of foods consumed
Carotenoids and flavonoids
Time frame: Change from baseline at up to 6 weeks
The plasma samples analysis will also include the measurement of carotenoids and flavonoids, which are present in watercress, and are related with antigenotoxic effects in vitro and have anti-proliferative effects, as demonstrated in several studies. Urine samples analysis will allow the measurement of flavonoids.
6 secondary outcomes
Cell phase angle 2
Time frame: change from 3 months at 3 years
body composition 2
Time frame: change from 3 months at 3 years
Quality of Life 2 (QoL2)
Time frame: change from 3 months at 3 years
Metabolomic profile 2
Time frame: change from 3 months at 3 years
Nutritional status 2
Time frame: change from 3 months at 3 years
Dietary intake 2
Time frame: change from 3 months at 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2015.
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Recruiting
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Long-term Effects of Cancer Treatment, Long-term Effects Secondary to Cancer Therapy in Adults
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.
Paula Ravasco, MD PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Watercress in people with Long-term Effects Secondary to Cancer Therapy in Adults, run by University of Lisbon at 1 site in Portugal.
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 1 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 11 Jun 2015. 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 Portugal. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Paula Ravasco, MD PhD (p.ravasco@medicina.ulisboa.pt), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cell phase angle (time frame: Change from baseline at up to 6 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jun 2015.