Miraculin for Taste Dysfunction in Head and Neck Cancer Patients

Overseen By Brittany Liu

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of California, San Francisco

Disqualifiers: Pre-existing dysgeusia, Tube feeds, Allergy to berries, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help head and neck cancer patients who experience taste changes due to radiation therapy. Researchers are testing whether a special fruit cube, known as miraculin (derived from the Miracle Fruit), can improve taste during the early stages of treatment. Participants will receive either the miracle fruit cube or a placebo cube for comparison. Ideal candidates have head and neck cancer, are undergoing radiation therapy, and have not experienced taste changes before starting treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that miraculin, found in miracle fruit, has been studied for its effects on taste problems in cancer patients. Some studies indicate it may help improve taste for those receiving chemotherapy. Importantly, safety tests on miraculin suggest it is safe when used to change the taste of sour foods.

Currently, the treatment is in a Phase 3 trial, which typically follows earlier research indicating general safety for people. While some side effects may still occur, previous studies suggest that miraculin is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for taste dysfunction?

Unlike the standard treatments for taste dysfunction in head and neck cancer patients, which often involve medications and therapies to manage symptoms, Miraculin is derived from the miracle fruit and offers a unique approach by temporarily altering taste perception. Researchers are excited about Miraculin because it has the potential to enhance taste sensations naturally without the typical side effects associated with pharmaceuticals. This could significantly improve the quality of life for patients by making food more palatable during a challenging time.

What evidence suggests that Miraculin might be an effective treatment for taste dysfunction?

Research has shown that miraculin, a substance in miracle fruit, may help improve taste for people with taste disorders. One study found that 23 patients with dysgeusia (a condition where taste is altered) experienced positive results with miraculin. Another study demonstrated that regular use of miraculin was both effective and safe for enhancing taste. These findings offer promise for head and neck cancer patients who experience taste changes due to radiation therapy. In this trial, participants will receive either miraculin or a placebo to evaluate its potential benefits for improving taste. While more research is needed, early evidence supports its potential benefits. ^{2 4 5 6 7}

Who Is on the Research Team?

Sue S. Yom

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with head and neck cancer, who can sign consent forms and have a performance status indicating they're mostly self-sufficient. They must be scheduled for radiation therapy, possibly with chemo, after surgery but cannot join if they had taste issues before treatment or rely on tube feeding.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

Ability to understand a written informed consent document, and the willingness to sign it

I have a confirmed diagnosis of head and neck cancer and have undergone surgery including neck dissection.

Exclusion Criteria

I cannot complete questionnaires in English.

You are allergic to berries.

I had changes in taste before starting radiation therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a miracle fruit cube or placebo cube three times a day before meals during radiation therapy

8 weeks

Weekly visits (in-person) for monitoring and product distribution

Follow-up

Participants are monitored for safety, effectiveness, and changes in taste function after treatment

24 weeks

Monthly visits (in-person) and regular virtual check-ins

What Are the Treatments Tested in This Trial?

Interventions

• Miracle Fruit Placebo Cube
• Miraculin

Trial Overview The study tests whether miraculin from miracle fruit can help patients undergoing radiation therapy maintain their sense of taste. Participants will receive either the miraculin cube or a placebo to see which one better prevents taste dysfunction during the first half of their treatment.

How Is the Trial Designed?

Group I: Miracle Fruit Experimental Treatment 1 Intervention

Participants will receive 1 Miracle Fruit Farm miracle fruit cube by mouth three times a day before meals

Group II: Miracle Fruit Placebo Placebo Group 1 Intervention

Participants will receive 1 placebo cube by mouth three times a day before meals

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Miracle Fruit Farm

Collaborator

Trials

1

Recruited

40+

Mount Zion Health Fund

Collaborator

Trials

13

Recruited

930+

Published Research Related to This Trial

In a pilot study involving eight cancer patients undergoing chemotherapy, the consumption of miracle fruit (Synsepalum dulcificum) significantly improved taste changes associated with treatment, enhancing food palatability.

All participants reported positive taste changes after using the miracle fruit supplement, suggesting it may be a beneficial supportive intervention for improving nutrition and quality of life during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of "miracle fruit" to improve food palatability for patients receiving chemotherapy. Wilken, MK., Satiroff, BA.[2012]

Miraculin, a protein from the miracle fruit, significantly enhances the pleasantness of acidic tastes in rhesus monkeys, as shown by preference tests where all acids tasted better after treatment.

The mechanism of miraculin involves altering taste perception by making taste receptors sensitive to acids, which normally do not taste sweet, effectively allowing them to signal sweetness through taste fibers that typically respond to sweet substances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The sweetness-inducing effect of miraculin; behavioural and neurophysiological experiments in the rhesus monkey Macaca mulatta. Brouwer, JN., Glaser, D., Hard Af Segerstad, C., et al.[2019]

The CLINMIR Protocol is a triple-blind, randomized, placebo-controlled trial involving 30 cancer patients to assess the effects of a miraculin-based food supplement on taste perception and nutritional status over three months.

The primary goal is to determine if regular consumption of the miracle berry supplement can improve taste perception in malnourished cancer patients, potentially leading to increased food intake and better nutritional outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Regular Consumption of a Miraculin-Based Food Supplement on Taste Perception and Nutritional Status in Malnourished Cancer Patients: A Triple-Blind, Randomized, Placebo-Controlled Clinical Trial-CLINMIR Pilot Protocol. López-Plaza, B., Gil, Á., Menéndez-Rey, A., et al.[2023]

Miracle berry contains a variety of phenolic compounds, with epicatechin being the most abundant at 17.8 mg/100g, which may contribute to its health benefits.

The flesh of the miracle berry exhibits strong antioxidant properties, effectively scavenging free radicals and inhibiting oxidation in fish oil, suggesting it could be a valuable addition to a health-promoting diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antioxidant-rich phytochemicals in miracle berry (Synsepalum dulcificum) and antioxidant activity of its extracts. Du, L., Shen, Y., Zhang, X., et al.[2014]

Miraculin (MCL) is a protein that can modify taste, making sour foods taste sweet, and this effect can last for over an hour after tasting sour solutions.

MCL appears to interact with the human sweet taste receptor by acting as an antagonist at neutral pH and switching to an agonist at acidic pH, suggesting its potential as a low-calorie sweetener for modifying flavors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular mechanisms of the action of miraculin, a taste-modifying protein. Misaka, T.[2013]

Momordicine-I (M-I), derived from bitter melon, effectively inhibits the growth of head and neck cancer cells in a dose-dependent manner while showing no toxicity to normal oral cells, suggesting a promising safety profile.

Mechanistically, M-I works by inhibiting the c-Met signaling pathway and its downstream targets, which leads to reduced tumor growth in mouse models, indicating its potential as a therapeutic agent against head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Momordicine-I, a Bitter Melon Bioactive Metabolite, Displays Anti-Tumor Activity in Head and Neck Cancer Involving c-Met and Downstream Signaling. Sur, S., Steele, R., Isbell, TS., et al.[2023]

In a study involving 62 post-radiotherapy head and neck cancer patients, both an edible saliva substitute (oral moisturizing jelly, OMJ) and a topical saliva gel (GC) significantly improved dry mouth symptoms and swallowing ability over 2 months.

The OMJ was found to be more effective than the GC in alleviating dry mouth and swallowing problems, which in turn positively impacted the patients' clinical nutritional status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alleviation of dry mouth by saliva substitutes improved swallowing ability and clinical nutritional status of post-radiotherapy head and neck cancer patients: a randomized controlled trial. Nuchit, S., Lam-Ubol, A., Paemuang, W., et al.[2022]

The study found that dysgeusia (taste alteration) significantly increased during treatment for head and neck cancer, peaking at week 7, but showed partial recovery in some dimensions after 6 months.

The use of a ginger-based supplement, Naumix/Naugin, appeared to reduce the incidence of grade 2 nausea to 12.9%, suggesting it may help mitigate nausea and related taste discomfort in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective assessment of taste impairment and nausea during radiotherapy for head and neck cancer. Martini, S., Iorio, GC., Arcadipane, F., et al.[2023]

Miracle berry (MB) has potential as a supplement for managing chronic diseases related to altered metabolism, such as obesity and insulin resistance, which are known risk factors for cancer.

MB is rich in antioxidants and has been shown to inhibit cancer cell proliferation and improve insulin resistance in vitro, suggesting it may help mitigate cancer risk through its effects on metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Miracle Berry as a Potential Supplement in the Control of Metabolic Risk Factors in Cancer. Gómez de Cedrón, M., Wagner, S., Reguero, M., et al.[2020]

The Miracle fruit plant (Synsepalum dulcificum) contains miraculin, a glycoprotein that modifies taste, and has been traditionally used in Africa for various medicinal purposes, showing potential benefits in managing diabetes, cholesterol levels, and cancer.

Scientific studies indicate that the plant is non-toxic at doses up to 200 mg/kg in rats, and it contains a variety of pharmacologically active compounds, suggesting it has significant therapeutic potential and nutritional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional benefits, phytochemical constituents, ethnomedicinal uses and biological properties of Miracle fruit plant (Synsepalum dulcificum Shumach. & Thonn. Daniell). Akinmoladun, AC., Adetuyi, AR., Komolafe, K., et al.[2021]

Synsepalum dulcificum, or miracle fruit, contains a glycoprotein called miraculin that modifies taste receptors, creating a sweet sensation when consuming acidic foods, which could be beneficial for people undergoing treatments that affect taste.

The fruit also shows promising antioxidant and anticancer properties, as well as potential antidiabetic effects observed in rat studies, suggesting it could be a healthy additive in diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical effects of Synsepalum dulcificum: a review. Swamy, KB., Hadi, SA., Sekaran, M., et al.[2014]

In a randomized, placebo-controlled trial involving 30 patients with head and neck cancer, SAMITAL® significantly reduced the severity of oral mucositis (OM) from day 31 until the end of treatment, while the placebo showed no significant improvement.

SAMITAL® not only provided effective pain relief starting from day 4 but also improved the quality of life for patients by enhancing their ability to eat, drink, and sleep, with no severe adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAMITAL® improves chemo/radiotherapy-induced oral mucositis in patients with head and neck cancer: results of a randomized, placebo-controlled, single-blind Phase II study. Pawar, D., Neve, RS., Kalgane, S., et al.[2021]

Transgenic tomato plants can produce high levels of miraculin, a protein that modifies sour tastes to sweet, with concentrations reaching up to 102.5 microg/g in leaves and 90.7 microg/g in fruits.

The recombinant miraculin from these tomatoes demonstrated strong sweetness-inducing activity comparable to that of native miraculin, suggesting that this method of production is effective and could serve as a sustainable alternative to sourcing from the native shrub.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetically stable expression of functional miraculin, a new type of alternative sweetener, in transgenic tomato plants. Sun, HJ., Kataoka, H., Yano, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10648678/

Effect of Regular Consumption of a Miraculin-Based Food ... Previous studies have shown the potential of miracle fruit for treating taste disorders. A pilot clinical trial involving 23 patients with dysgeusia derived ...

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05273307

Addressing Taste Dysfunction With Miraculin in Head and ... To determine if the use of miracle fruit during radiation therapy for head and neck cancer patients can reduce the effect of subjective taste alteration ...

3. medrxiv.org medrxiv.org/content/10.1101/2024.05.15.24307453v1.full

Efficacy and Safety of Habitual Consumption of a Food ... These results suggest that habitual consumption of a standard dose of 150 mg of miraculin–food supplement (DMB) is effective and safe for ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-01711

Miraculin for Improving Taste Dysfunction in Head and ... This phase III trial tests whether miraculin, also called “Miracle Fruit,” works in improving taste dysfunction in patients with head and neck cancer ...

5. withpower.com withpower.com/trial/phase-3-taste-dysfunction-4-2022-17deb

Miraculin for Taste Dysfunction in Head and Neck Cancer ... This trial tests if miracle fruit cubes can help head and neck cancer patients undergoing radiation therapy by improving their sense of taste.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11207068/

The CLINMIR Pilot Study - PMC - PubMed Central Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life.

7. science.food.gov.uk science.food.gov.uk/article/131823-safety-assessment-of-dried-miracle-berry-_synsepalum-dulcificum_-as-a-novel-food-for-use-in-food-and-food-supplements-rp1351

Safety Assessment of Dried Miracle Berry (Synsepalum ... This new application is seeking to use the novel food as a functional food supplement to modify the taste of sour foods due to the presence of miraculin.