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| ID | Type | Description | Link |
|---|---|---|---|
| 2018NTLS144 | Other Identifier | University of Minnesota Masonic Cancer Center |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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The goal of this research is to determine if consuming one of two study drinks will help enhance the detoxification of multiple environmental toxicants and cancer causing agents, particularly in subjects who are null for glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), or both. If our research supports this idea, this drink could be an inexpensive dietary component, which could promote good health.
Volatile organic carcinogens and toxicants are ubiquitous environmental and endogenous compounds to which virtually all humans are exposed. All of these compounds are detoxified by metabolic processes that ultimately result in conjugation with glutathione and excretion of mercapturic acids in urine. Glutathione conjugation can be upregulated by isothiocyanates through the Nrf2 pathway and related routes of metabolism. This study will examine if watercress consumption, resulting in exposure to milligram amounts of 2-phenethyl isothiocyanate (PEITC) per day, will enhance the detoxification of benzene, acrolein and other related volatile toxicants and carcinogens. One of the two drinks contains PEITC released from freeze dried watercress while the other drink contains maltodextrin.
Benzene causes acute myeloid leukemia/acute non-lymphocytic leukemia in humans, and a positive association has been observed between benzene exposure and acute lymphocytic leukemia, chronic lymphocytic leukemia, multiple myeloma, and non-Hodgkin lymphoma. Acrolein is highly toxic and causes nasal tumors in rats. Benzene is classified as "carcinogenic to humans" by the International Agency for Research on Cancer, and acrolein as "probably carcinogenic to humans." Mercapturic acids of the volatile toxicants and carcinogens propylene oxide, crotonaldehyde, methyl vinyl ketone, methacrolein, and acrylonitrile will also be quantified.
The study will be a randomized, placebo-controlled, single-blind, phase II clinical trial with a crossover study design. Participants will be assigned to active (freeze dried watercress) or placebo (maltodextrin) study product for 14 days, then undergo a 4-week wash-out period, and will then be crossed over to the other product for another 14 days. During the treatment phase, subjects will consume the watercress beverage or placebo, three times per day. The target dose will be 40 mg/day of PEITC. Subjects may be titrated down if they report being unable to tolerate the full dose. Urine, oral swabs, and saliva will be collected.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Freeze Dried Watercress Preparation | Experimental |
| |
| Placebo Preparation | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Freeze Dried Watercress Preparation | Dietary Supplement | Freeze dried watercress containing gluconasturtiin, which when added to provided water with flavor powder, will result in a total target dose of up to 40 mg/day of 2-phenethyl isothiocyanate (PEITC). Preparation consumed at breakfast, lunch and dinner 3x daily for 2 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Carcinogen Detoxification of Metabolites in Urine. | Carcinogen detoxification metabolites in urine. Biomarkers to be analyzed: 2-cyanoethyl mercapturic acid (CEMA), 3-hydroxypropyl mercapturic acid (HPMA1), 2-hydroxypropyl mercapturic acid (HPMA2), phenyl mercapturic acid (SPMA), 3-hydroxy-1-methylpropyl mercapturic acid (HMPMA1), 3-hydroxy-2-methylpropyl mercapturic acid (HMPMA2), and 3-hydroxy-3-methylpropyl mercapturic acid (HMPMA3), | 2 Months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dorothy Hatsukami, PhD | University of Minnesota | Principal Investigator |
| Stephen Hecht, PhD | Department of Laboratory Medicine and Pathology, University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Minnesota | Minneapolis | Minnesota | 55405 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41699775 | Derived | Hecht SS, Carmella SG, Basu S, Chen M, Wittman M, Tang MK, Zhao Y, Lu J, Ng D, Heath E, Fujioka N, Egbert A, Strayer L, Usman A, Thomson NM, Murphy SE, Hatsukami DK. A watercress drink increases detoxification of common environmental carcinogens such as acrolein and benzene: results of a randomized clinical trial. Carcinogenesis. 2025 Dec 26;47(1):bgag007. doi: 10.1093/carcin/bgag007. |
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300 participants randomized to treatment arms. 188 analyzed for study objectives.
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| ID | Title | Description |
|---|---|---|
| FG000 | Freeze Dried Watercress Preparation Then Placebo | Participants were randomly assigned to the watercress then placebo arm. During the treatment phase, participants consumed the watercress beverage 3 times per day (around the time of breakfast, lunch and dinner) for 14 days. Participants had a 4-week washout period before switching to the placebo beverage for 14 days. The placebo was consumed in the same pattern 3 times per day around meals as the watercress beverage. |
| FG001 | Placebo Then Freeze Dried Watercress Preparation | Participants were randomly assigned to the placebo then watercress arm. During the treatment phase, participants consumed the placebo beverage, 3 times per day (around the time of breakfast, lunch and dinner) for 14 days. Participants had a 4-week washout period before switching to the watercress beverage for 14 days. The watercress beverage was consumed in the same pattern 3 times per day around meals as the placebo beverage. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Freeze Dried Watercress Preparation Then Placebo | Participants were randomly assigned to the watercress then placebo arm. During the treatment phase, participants consumed the watercress beverage 3 times per day (around the time of breakfast, lunch and dinner) for 14 days. Participants had a 4-week washout period before switching to the placebo beverage for 14 days. The placebo was consumed in the same pattern 3 times per day around meals as the watercress beverage. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Carcinogen Detoxification of Metabolites in Urine. | Carcinogen detoxification metabolites in urine. Biomarkers to be analyzed: 2-cyanoethyl mercapturic acid (CEMA), 3-hydroxypropyl mercapturic acid (HPMA1), 2-hydroxypropyl mercapturic acid (HPMA2), phenyl mercapturic acid (SPMA), 3-hydroxy-1-methylpropyl mercapturic acid (HMPMA1), 3-hydroxy-2-methylpropyl mercapturic acid (HMPMA2), and 3-hydroxy-3-methylpropyl mercapturic acid (HMPMA3), | Number analyzed differs due to incomplete markers in analysis. | Posted | Median | Inter-Quartile Range | ng/mL | 2 Months |
|
2 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Freeze Dried Watercress | Freeze dried watercress containing gluconasturtiin, which when added to provided water with flavor powder, will result in a total target dose of up to 40 mg/day of 2-phenethyl isothiocyanate (PEITC). Preparation consumed at breakfast, lunch and dinner 3x daily for 2 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Saliva, changes in | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dorothy Hatsukami, PhD | Masonic Cancer Center | (612) 626-2121 | hatsu001@umn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 23, 2020 | Jun 16, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Sep 15, 2022 | Jun 17, 2025 | ICF_001.pdf |
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| Placebo Preparation | Dietary Supplement | Maltodextrin added to provided water with flavor powder. Preparation consumed at breakfast, lunch and dinner 3x daily for 2 weeks. |
|
| BG001 | Placebo Then Freeze Dried Watercress Preparation | Participants were randomly assigned to the placebo then watercress arm. During the treatment phase, participants consumed the placebo beverage, 3 times per day (around the time of breakfast, lunch and dinner) for 14 days. Participants had a 4-week washout period before switching to the watercress beverage for 14 days. The watercress beverage was consumed in the same pattern 3 times per day around meals as the placebo beverage. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | Maltodextrin added to provided water with flavor powder. Preparation consumed at breakfast, lunch and dinner 3x daily for 2 weeks. |
|
|
| 0 |
| 300 |
| 0 |
| 300 |
| 188 |
| 300 |
| EG001 | Placebo | Maltodextrin added to provided water with flavor powder. Preparation consumed at breakfast, lunch and dinner 3x daily for 2 weeks. | 0 | 300 | 0 | 300 | 50 | 300 |
| Oral dysesthesia (burning/tingling/numbness/pain) | General disorders | Systematic Assessment |
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| Mouth Sore | General disorders | Systematic Assessment |
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| Dyspepsia (upset stomach) | Gastrointestinal disorders | Systematic Assessment |
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| Gastroesophageal Reflux (GERD/heartburn/acid) | Gastrointestinal disorders | Systematic Assessment |
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| Stomach Pain | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | General disorders | Systematic Assessment |
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| Bloating | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Increased gas, belching and changes to stool | Gastrointestinal disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Vivid Dreams (see S for nightmare/terror) | General disorders | Systematic Assessment |
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| Appetite, Loss of | General disorders | Systematic Assessment |
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| Appetite, Increase/hunger | General disorders | Systematic Assessment |
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| Myalgia (muscle aches/pain/spasms) | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Dizziness/Lightheadedness | General disorders | Systematic Assessment |
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| Dysgeusia (change in taste/smell) | General disorders | Systematic Assessment |
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| Headache (incl. migraine) | General disorders | Systematic Assessment |
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| Depressed (sad) mood | Psychiatric disorders | Systematic Assessment |
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| Nightmare/terror | General disorders | Systematic Assessment |
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| Confusion | Psychiatric disorders | Systematic Assessment |
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| Increased Urination | Gastrointestinal disorders | Systematic Assessment |
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| Nasal congestion (incl. runny nose) | General disorders | Systematic Assessment |
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| Rash | General disorders | Systematic Assessment |
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| Hot Flashes | General disorders | Systematic Assessment |
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| Edema (face/neck/limbs/trunk/localized) | General disorders | Systematic Assessment |
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| Pain (other) | General disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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