Colorectal CancerEarly Phase 1NCT06887673
Lipid Mediators & Cancer: Montelukast, SPM, and Almonds
A Early Phase 1 study testing Sports Pro Resolve 4 g, Double Wood SPM 4 g and 20 California Sweet Almonds in people with Colorectal Cancer and Sarcoma, run by University of South Florida at 2 sites in United States.
Trial summary
The purpose of this study is to create a prospective investigation to examine the effects of montelukast, almonds/almond oil, and specialized pro-resolving mediators (SPMs) on lipid profiles and tumor-associated macrophages (TAMs) in cancer patients (colorectal cancer, sarcoma, brain tumors, endometrial cancer, and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Sarcoma, Brain Tumors
- What is being tested?
- Sports Pro Resolve 4 g, Double Wood SPM 4 g and 20 California Sweet Almonds
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2025to Mar 2026
- Phase
- Early Phase 1
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed individuals with stages I-IV colorectal or ovarian cancer, grade 1 and 2 endometrial cancer, as well as those with brain tumors or sarcoma.
- Participants scheduled for surgical intervention at least two (2) weeks from the day of enrollment.
- Patients must be able to understand and willing to sign a written informed consent document for both this study and the University of South Florida (USF)/ Tampa General Hospital (TGH) Biorepository study (STUDY000356).
- Age 18 or older.
Who cannot join
- Inability to give consent due to a mental condition that makes the participant unable to understand the study's nature, scope, and possible consequences.
- Participants who are unlikely to adhere to the protocol as determined by the study investigator.
- Allergy to fish, seafood, aspirin, NSAIDs, montelukast, or nuts
- Participants with a history of asthma or chronic obstructive pulmonary disease (COPD).
- Patients with a history of phenylketonuria (PKU).
- Participants with a history of a psychiatric illness (e.g., major depression, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, etc.).
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- Surgical intervention scheduled more than eight (8) weeks from the initial enrollment day.
- No evidence of a discrete mass on endoscopy or radiologic imaging
- Concomitant existence of other malignancies
- Uncontrolled hypertension or diabetes mellitus
- Chronic Liver Disease or cirrhosis
- Liver function impairment or persisting elevations (confirmed by retest) of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or direct bilirubin greater than 2x the upper limit of the normal range (ULN)
- Bleeding conditions such as disorders of platelet function, idiopathic thrombocytopenia purpura (ITP), thrombotic thrombocytopenic purpura (TTP), hemophilia or any clotting factor deficiency, von Willebrand disease or Glanzmann disease among other
- Use of antiplatelet or anticoagulant medications, including aspirin, clopidogrel, warfarin, direct oral anticoagulants (DOACs), and heparin, among others
- Persistent significant or severe infection, either acute or chronic
- Participants with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia (confirmed by retest):
- Hematocrit < 35% and/or
- Absolute white blood cell count < 3000 cells/mm3 (μL) and/or
- Platelet count < 150 000 cells/mm3 (μL) and/or
- Absolute neutrophil ≤ 1500 cells/mm3 (μL)
- Chronic use of immunosuppressive medications
- History of organ transplantation
- Emergency surgery
- Pregnant or breast-feeding women or those who plan to become pregnant during the study.
- Women of childbearing potential who are not protected by effective contraceptive methods of birth control and/or are unwilling or unable to be tested for pregnancy.
- Prisoners
- Participants who have received treatment with leukotriene inhibitors, taken omega-3 supplements, or eaten almonds within the last 4 weeks.
- Prior use of any investigational drug in the preceding six (6) months
- Participants who, after being enrolled in this study and assigned a particular study treatment, consume products involved in other study cohorts other than what they were assigned (i.e. if a patient is assigned to take SPMs as their study treatment but during the course of the study also is consuming daily almonds)
- Participants who are unable to swallow oral medication or chew almonds.
- Participants who have already started neoadjuvant therapies for their cancer diagnosis
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Beth Montera contact
United States2 sites
Tampa General Hospital
Tampa, Florida, 33606
Avennette Pinto, 813-505-4787, apinto3@usf.edu
Beth Montera, bmontera@usf.edu
University of South Florida
Tampa, Florida, 33606
Avennette Pinto, 813-505-4787, apinto3@usf.edu
Beth Montera, bmontera@usf.edu
About this study
Official title: Exploring the Impact of Montelukast, SPM, and/or Almond/Almond Oil Supplementation on Lipid Mediator Biosynthesis in Colorectal, Sarcomas, Brain Tumors, Endometrial, and Ovarian Cancer: A Pilot Study
The purpose of this study is to create a prospective investigation to examine the effects of montelukast, almonds/almond oil, and specialized pro-resolving mediators (SPMs) on lipid profiles and tumor-associated macrophages (TAMs) in cancer patients (colorectal cancer, sarcoma, brain tumors, endometrial cancer, and ovarian cancer). The focus will be on assessing changes in lipid mediator concentrations, TAM reprogramming, and immune cell function in treated versus untreated patients. It is hypothesized that montelukast will reduce the pro-inflammatory effects of leukotriene B4 (LTB4), while SPMs and almonds/almond oil will shift the balance toward pro-resolving mediators, enhancing anti-inflammatory and immune-stimulatory responses and reprogramming TAMs.
Read the detailed description
This prospective study investigates the effects of montelukast, almonds/almond oil, and specialized pro-resolving mediators (SPMs) on lipid profiles and tumor-associated macrophages (TAMs) in patients with colorectal cancer (CRC), sarcoma, brain tumors (BT), endometrial cancer (EC), and ovarian cancer (OvCa). Patients receiving these treatments will be compared to untreated controls, with tissue samples collected post-surgery for analysis. A cohort of patients who have undergone tumor resection will be included for the assessment of lipid mediator concentrations (approximately 65 arachidonic acid pathway lipids) and TAM reprogramming, with an emphasis on comparing treated and untreated groups. The study will also examine peripheral blood mononuclear cells (PBMCs) and plasma concentrations of lipid mediators before and after treatment, focusing on changes in PBMC function and phenotype. It is hypothesized that montelukast, an LTB4/ cysteinyl leukotriene receptor 1 (CYSLTR1) inhibitor, will reduce the pro-inflammatory effects of LTB4 in cancer tissues. Furthermore, it is anticipated that SPMs and almonds/almond oil will shift the lipid mediator balance toward pro-resolving mediators, enhancing anti-inflammatory responses, stimulating immune function, and reprogramming TAMs.
- Conditions
- Colorectal Cancer, Sarcoma, Brain Tumors, Endometrial Cancer, Ovarian Cancer
- Being tested
- No Interventions, Sports Pro Resolve 4 g, Double Wood SPM 4 g, 20 California Sweet Almonds, Montelukast 10 Mg Oral Tablet
- Keywords
- Montelukast, Almonds/Almond oil, Specialized pro-resolving mediators, Tumor-associated macrophages, Lipid mediators, Colorectal cancer, Inflammation
- Medical subject headings
- Colorectal Neoplasms, Sarcoma, Brain Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No InterventionsOther
No study treatment other than the standard of care management.
Sports Pro Resolve 4 gDietary supplement
Sports Pro Resolve 4 tabs (2 g) twice daily
Double Wood SPM 4 gDietary supplement
Double Wood SPM 4 tabs (2 g) twice daily
20 California Sweet AlmondsDietary supplement
10 California Sweet Almonds twice daily
Montelukast 10 Mg Oral TabletDrug
Montelukast 10 Mg Oral Tablet daily
Montelukast 10 Mg Oral Tablet and SPM 4 gCombination product
Montelukast 10 Mg Oral Tablet and SPM 4 g
Cold- Pressed Almond Oil 30 mLDietary supplement
Cold- Pressed Almond Oil 30 mL every morning
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (Control) | Other | ARM 1: Participants in this arm will receive no study treatment other than the standard of care management for their cancer. Receives: Other: No Interventions |
| Arm 2A: Sports Pro Resolve 4 g | Experimental | ARM 2A: Participants in this arm will receive 4 tabs (2 g) in the morning and 4 tabs (2 g) in the evening for 2 weeks before surgery. Receives: Dietary Supplement: Sports Pro Resolve 4 g |
| Arm 2B: Double Wood SPM 4 g | Experimental | ARM 2B: Participants in this arm will receive 4 tabs (2 g) in the morning and 4 tabs (2 g) in the evening for 2 weeks before surgery. Receives: Dietary Supplement: Double Wood SPM 4 g |
| Arm 3: California Sweet Almonds- 20 (Skin-on, Unsalted and Unprocessed) | Experimental | ARM 3: Participants in this arm will receive 20 skin-on, unsalted, unprocessed California Sweet Almonds, consumed as 10 almonds twice per day, for 2 weeks prior to surgery. Receives: Dietary Supplement: 20 California Sweet Almonds |
| Arm 4: Montelukast 10 mg | Experimental | ARM 4: Participants in this arm will receive Montelukast 10 mg orally daily for 2 weeks before surgery. Receives: Drug: Montelukast 10 Mg Oral Tablet |
| Arm 5: Montelukast 10 mg and SPM supplement 4 g | Experimental | ARM 5: Participants in this arm will receive a combination of Montelukast 10 mg daily and the determined SPM supplement 4 g daily, depending on which supplement produce the most SPMs in plasma. Receives: Combination Product: Montelukast 10 Mg Oral Tablet and SPM 4 g |
| Arm 6: Cold-Pressed Almond Oil 30 milliliter | Experimental | ARM 6; Participants in this arm will receive 30 milliliter of cold-pressed almond oil every morning with breakfast for 2 weeks before surgery Receives: Dietary Supplement: Cold- Pressed Almond Oil 30 mL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantity of lipid mediators in a tumor specimen after 2 weeks of study treatment.
Quantitation will be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). The absolute quantity of these lipid mediators will be compared to the absolute quantity in the corresponding normal tissue. In preliminary studies, the investigators have used LC-MS/MS to measure ~65 different lipid mediators of the arachidonic acid pathway in colorectal cancer. Interestingly, the investigators found high proportions of pro-inflammation mediators and depressed levels of pro-resolution-of-inflammation mediators in cancer tissue compared with the non-affected tissue of the same patients. Possible study treatments include: specialized pro-resolving mediators vs Montelukast vs almonds/almond oil vs combination).
Measured: Day 14 of treatment
Quantity of lipid mediators in a non-cancerous (i.e. normal) tissue from the resected surgical specimen after 2 weeks of study treatment.
Quantitation will be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). The absolute quantity of these lipid mediators will be compared to the absolute quantity in the corresponding cancer tissue. This change in quantity will enable us to make deductions about the influence of the corresponding study treatment on the tumor and its environment. For example, does the treatment in question make the tumor environment less inflamed/promote healing and therefore make the cancer more susceptible to treatment? Possible study treatments include: specialized pro-resolving mediators vs Montelukast vs almonds/almond oil vs combination).
Measured: Day 14 of treatment
Secondary outcomes (4)
Quantity of tumor microenvironment subpopulations in a tumor specimen versus corresponding normal tissue after 2 weeks of study treatment.
Tumor microenvironment subpopulations are defined as the various components of the immune system in the tissue surrounding a cancer, i.e.: cluster of differentiation 4 (CD4) T cells, cluster of differentiation 8 (CD8) T cells, B cells, natural killer (NK) cells, macrophages, etc. Quantitation will be assessed using n-counter analysis.
Measured: Day 14 of treatment
Distribution of tumor-associated macrophage (TAM) phenotype in tumor specimens versus corresponding normal tissue after 2 weeks of study treatment.
There are two main TAM phenotypes: M1 and M2. M1 are the classically activated, anti-tumor macrophages, and M2 are the "bad", pro-inflammation/neoplastic macrophages. Change in distribution will be assessed using multiparameter flow cytometry. M1 versus M2 phenotypes will be identified by utilizing macrophage-specific biomarkers.
Measured: Day 14 of treatment
Functionality of tumor-associated macrophages in tumor specimens versus corresponding normal tissue after 2 weeks of study treatment.
Change in functionality will be determined using efferocytosis assays.
Measured: Day 14 of treatment
Change in quantity of lipids in peripheral blood from day 0 to day 14 of study treatment.
Quantitation will be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS). This assessment will enable us to correlate peripheral blood levels of lipid mediators with tissue penetrance. For example, the investigators may find that a study treatment has a significant impact on the lipid mediator profile of the blood but that same impact is not seen in the corresponding tissue of that patient; therefore, there deductions can be made about tissue penetrance capability.
Measured: Day 0 and Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2025
- Study startMar 2025 (estimated)
- Primary completionMar 2026 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (44)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of South Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jorge Marcet, Principal investigator, University of South Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06887673
- Sponsor's protocol ID
- STUDY006089
- Status last verified
- Mar 2025
- First submitted
- 25 Feb 2025
- Last updated
- 20 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Prasad S, Sung B, Aggarwal BB. Age-associated chronic diseases require age-old medicine: role of chronic inflammation. Prev Med. 2012 May;54 Suppl(Suppl):S29-37. doi: 10.1016/j.ypmed.2011.11.011. Epub 2011 Dec 9.
PubMed 22178471Serhan CN. Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology. Mol Aspects Med. 2017 Dec;58:1-11. doi: 10.1016/j.mam.2017.03.001. Epub 2017 Mar 3.
PubMed 28263773Song M, Zhang X, Meyerhardt JA, Giovannucci EL, Ogino S, Fuchs CS, Chan AT. Marine omega-3 polyunsaturated fatty acid intake and survival after colorectal cancer diagnosis. Gut. 2017 Oct;66(10):1790-1796. doi: 10.1136/gutjnl-2016-311990. Epub 2016 Jul 19.
PubMed 27436272Daniel CR, McCullough ML, Patel RC, Jacobs EJ, Flanders WD, Thun MJ, Calle EE. Dietary intake of omega-6 and omega-3 fatty acids and risk of colorectal cancer in a prospective cohort of U.S. men and women. Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):516-25. doi: 10.1158/1055-9965.EPI-08-0750. Epub 2009 Feb 3.
PubMed 19190143Shin A, Cho S, Sandin S, Lof M, Oh MY, Weiderpass E. Omega-3 and -6 Fatty Acid Intake and Colorectal Cancer Risk in Swedish Women's Lifestyle and Health Cohort. Cancer Res Treat. 2020 Jul;52(3):848-854. doi: 10.4143/crt.2019.550. Epub 2020 Mar 6.
PubMed 32138465Schloss I, Kidd MS, Tichelaar HY, Young GO, O'Keefe SJ. Dietary factors associated with a low risk of colon cancer in coloured west coast fishermen. S Afr Med J. 1997 Feb;87(2):152-8.
PubMed 9107220Petrik MB, McEntee MF, Chiu CH, Whelan J. Antagonism of arachidonic acid is linked to the antitumorigenic effect of dietary eicosapentaenoic acid in Apc(Min/+) mice. J Nutr. 2000 May;130(5):1153-8. doi: 10.1093/jn/130.5.1153.
PubMed 10801912Fini L, Piazzi G, Ceccarelli C, Daoud Y, Belluzzi A, Munarini A, Graziani G, Fogliano V, Selgrad M, Garcia M, Gasbarrini A, Genta RM, Boland CR, Ricciardiello L. Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in Apc(Min/+) mice. Clin Cancer Res. 2010 Dec 1;16(23):5703-11. doi: 10.1158/1078-0432.CCR-10-1990. Epub 2010 Oct 28.
PubMed 21030497Nowak J, Weylandt KH, Habbel P, Wang J, Dignass A, Glickman JN, Kang JX. Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids. Carcinogenesis. 2007 Sep;28(9):1991-5. doi: 10.1093/carcin/bgm166. Epub 2007 Jul 18.
PubMed 17634405West NJ, Clark SK, Phillips RK, Hutchinson JM, Leicester RJ, Belluzzi A, Hull MA. Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut. 2010 Jul;59(7):918-25. doi: 10.1136/gut.2009.200642. Epub 2010 Mar 26.
PubMed 20348368Liang B, Wang S, Ye YJ, Yang XD, Wang YL, Qu J, Xie QW, Yin MJ. Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients. World J Gastroenterol. 2008 Apr 21;14(15):2434-9. doi: 10.3748/wjg.14.2434.
PubMed 18416476Sorensen LS, Thorlacius-Ussing O, Rasmussen HH, Lundbye-Christensen S, Calder PC, Lindorff-Larsen K, Schmidt EB. Effects of perioperative supplementation with omega-3 fatty acids on leukotriene B(4) and leukotriene B(5) production by stimulated neutrophils in patients with colorectal cancer: a randomized, placebo-controlled intervention trial. Nutrients. 2014 Sep 29;6(10):4043-57. doi: 10.3390/nu6104043.
PubMed 25268838Manda K, Kriesen S, Hildebrandt G, Fietkau R, Klautke G. Omega-3 fatty acid supplementation in cancer therapy : does eicosapentanoic acid influence the radiosensitivity of tumor cells? Strahlenther Onkol. 2011 Feb;187(2):127-34. doi: 10.1007/s00066-010-2166-6. Epub 2011 Jan 18.
PubMed 21267532West L, Yin Y, Pierce SR, Fang Z, Fan Y, Sun W, Tucker K, Staley A, Zhou C, Bae-Jump V. Docosahexaenoic acid (DHA), an omega-3 fatty acid, inhibits tumor growth and metastatic potential of ovarian cancer. Am J Cancer Res. 2020 Dec 1;10(12):4450-4463. eCollection 2020.
PubMed 33415010Kuznetsova L, Chen J, Sun L, Wu X, Pepe A, Veith JM, Pera P, Bernacki RJ, Ojima I. Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates as promising anticancer agents. Bioorg Med Chem Lett. 2006 Feb 15;16(4):974-7. doi: 10.1016/j.bmcl.2005.10.089. Epub 2005 Nov 18.
PubMed 16298526