Lipid Mediators & Cancer: Montelukast, SPM, and Almonds

University of South Florida

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Endometrial Cancer; Sarcoma; Brain Tumors; Ovarian Cancer; Colorectal Cancer

Treatments: Dietary Supplement: Sports Pro Resolve 4 g; Dietary Supplement: Double Wood SPM 4 g; Combination Product: Montelukast 10 Mg Oral Tablet and SPM 4 g; Other: No Interventions; Dietary Supplement: 20 California Sweet Almonds; Dietary Supplement: Cold- Pressed Almond Oil 30 mL; Drug: Montelukast 10 Mg Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT06887673

STUDY006089

Details and patient eligibility

About

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.

Full 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.

Enrollment: 56 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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.
2. Participants scheduled for surgical intervention at least two (2) weeks from the day of enrollment.
3. 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).
4. Age 18 or older.

Exclusion criteria

1. Inability to give consent due to a mental condition that makes the participant unable to understand the study's nature, scope, and possible consequences.

2. Participants who are unlikely to adhere to the protocol as determined by the study investigator.

3. Allergy to fish, seafood, aspirin, NSAIDs, montelukast, or nuts

4. Participants with a history of asthma or chronic obstructive pulmonary disease (COPD).

5. Patients with a history of phenylketonuria (PKU).

6. Participants with a history of a psychiatric illness (e.g., major depression, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, etc.).

7. Surgical intervention scheduled more than eight (8) weeks from the initial enrollment day.

8. No evidence of a discrete mass on endoscopy or radiologic imaging

9. Concomitant existence of other malignancies

10. Uncontrolled hypertension or diabetes mellitus

11. Chronic Liver Disease or cirrhosis

12. 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)

13. 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

14. Use of antiplatelet or anticoagulant medications, including aspirin, clopidogrel, warfarin, direct oral anticoagulants (DOACs), and heparin, among others

15. Persistent significant or severe infection, either acute or chronic

16. Participants with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia (confirmed by retest):

    1. Hematocrit < 35% and/or
    2. Absolute white blood cell count < 3000 cells/mm3 (μL) and/or
    3. Platelet count < 150 000 cells/mm3 (μL) and/or
    4. Absolute neutrophil ≤ 1500 cells/mm3 (μL)

17. Chronic use of immunosuppressive medications

18. History of organ transplantation

19. Emergency surgery

20. Pregnant or breast-feeding women or those who plan to become pregnant during the study.

21. 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.

22. Prisoners

23. Participants who have received treatment with leukotriene inhibitors, taken omega-3 supplements, or eaten almonds within the last 4 weeks.

24. Prior use of any investigational drug in the preceding six (6) months

25. 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)

26. Participants who are unable to swallow oral medication or chew almonds.

27. Participants who have already started neoadjuvant therapies for their cancer diagnosis

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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56 participants in 7 patient groups

Arm 1 (Control)

Other group

Description:

ARM 1: Participants in this arm will receive no study treatment other than the standard of care management for their cancer.

Treatment:

Other: No Interventions

Arm 2A: Sports Pro Resolve 4 g

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Sports Pro Resolve 4 g

Arm 2B: Double Wood SPM 4 g

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Double Wood SPM 4 g

Arm 3: California Sweet Almonds- 20 (Skin-on, Unsalted and Unprocessed)

Experimental group

Description:

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.

Treatment:

Dietary Supplement: 20 California Sweet Almonds

Arm 4: Montelukast 10 mg

Experimental group

Description:

ARM 4: Participants in this arm will receive Montelukast 10 mg orally daily for 2 weeks before surgery.

Treatment:

Drug: Montelukast 10 Mg Oral Tablet

Arm 5: Montelukast 10 mg and SPM supplement 4 g

Experimental group

Description:

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.

Treatment:

Combination Product: Montelukast 10 Mg Oral Tablet and SPM 4 g

Arm 6: Cold-Pressed Almond Oil 30 milliliter

Experimental group

Description:

ARM 6; Participants in this arm will receive 30 milliliter of cold-pressed almond oil every morning with breakfast for 2 weeks before surgery

Treatment:

Dietary Supplement: Cold- Pressed Almond Oil 30 mL