Miraculin for Taste Dysfunction in Head and Neck Cancer Patients

Overseen By Jamese Johnson

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

Trial Summary

What is the purpose of this trial?

This trial tests if miracle fruit cubes can help head and neck cancer patients undergoing radiation therapy by improving their sense of taste, making it easier for them to eat and maintain nutrition.

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.

What data supports the effectiveness of the treatment Miraculin for taste dysfunction in head and neck cancer patients?

Research shows that the miracle fruit, which contains miraculin, can improve taste perception in cancer patients undergoing chemotherapy, making food taste better and potentially improving nutrition. A pilot study found that patients reported positive taste changes when using a miraculin-based supplement. ^{1 2 3 4 5}

Is Miraculin safe for human use?

Miraculin, found in the miracle berry, has been used traditionally in Africa and studied for its health benefits, including antioxidant and antidiabetic effects. Studies have shown that it is not toxic in rats at certain doses, suggesting it may be safe for human use, but more research is needed to confirm this. ^{6 7 8 9 10}

How does the treatment Miraculin differ from other treatments for taste dysfunction in head and neck cancer patients?

Miraculin is unique because it is a protein from the miracle fruit that can change sour tastes into sweet ones, helping to improve the taste of food for cancer patients experiencing taste changes. Unlike other treatments, it works by modifying taste perception, potentially improving nutrition and quality of life for patients undergoing chemotherapy. ^{1 4 11 12 13}

Research Team

Sue S. Yom

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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.

I am 18 years old or older.

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

Exclusion Criteria

I cannot complete questionnaires in English.

You are allergic to berries.

I had changes in taste before starting radiation therapy.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pilot study of "miracle fruit" to improve food palatability for patients receiving chemotherapy. [2012]

2. Germany 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Prospective assessment of taste impairment and nausea during radiotherapy for head and neck cancer. [2023]

4. Switzerland 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. [2023]

5. Germany 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Antioxidant-rich phytochemicals in miracle berry (Synsepalum dulcificum) and antioxidant activity of its extracts. [2014]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Miracle Berry as a Potential Supplement in the Control of Metabolic Risk Factors in Cancer. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Nutritional benefits, phytochemical constituents, ethnomedicinal uses and biological properties of Miracle fruit plant (Synsepalum dulcificum Shumach. & Thonn. Daniell). [2021]

9. United States pubmed.ncbi.nlm.nih.gov

The clinical effects of Synsepalum dulcificum: a review. [2014]

10. Switzerland 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. [2023]

11. England pubmed.ncbi.nlm.nih.gov

The sweetness-inducing effect of miraculin; behavioural and neurophysiological experiments in the rhesus monkey Macaca mulatta. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Genetically stable expression of functional miraculin, a new type of alternative sweetener, in transgenic tomato plants. [2022]

13. England pubmed.ncbi.nlm.nih.gov

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