Effect of Dried Miracle Berry on the Olfactory-gustative Perception in Malnourished Cancer Patients

NCT ID: NCT05486260

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-23
• Study Completion Date: 2023-09-30

Brief Summary

Cancer is one of the main causes of death globally, being in many countries the first cause of mortality. One of the main side effects of chemotherapy and/or radiotherapy treatment in cancer patients is the alteration of taste and smell, internationally known as these anomalies Taste Smell Alterations (TSA). These alterations are the result of an altered cellular structure, the presence of TSA is associated with reduced quality of life and poor nutrition, due to dietary changes made by these patients.

Synsepalum dulcidicum (dried miracle berry, DMB) is a plant belonging to the Sapotaceae family, made up of around 800 species grouped into around 40 genera. It is an indigenous species to the forest regions of West Africa. Nuts of this specie have been approved as a novel food in accordance with Regulation (EU) 2015/2238 and at the request of the European Commission through the European Food Safety Authority (EFSA) Panel on Nutrition, Novel Foods and Food Allergens. The characteristic component of DMB is miraculin. Miraculin is a glycoprotein whose consumption causes acidic and sour foods, and to a lesser extent bitter, to be perceived as having a sweet taste. In this sense, it is possible that the consumption of DMB before each meal can improve sensory perception after treatment with chemotherapy or radiotherapy.

Detailed Description

Randomized, parallel, triple-blind, controlled clinical trial to evaluate the effect of habitual consumption of DMB on the olfactory-gustative perception in cancer patients with malnutrition.

30 volunteers will be recruited at the La Paz University Hospital of Madrid. Participants should meet the next inclusion criteria: men and women over 18, a weight loss >=5 %, malnutrition, taste alterations, cancer patients treated with neoadjuvant chemotherapy prior to surgery, chemotherapy or chemo-radiotherapy who are not candidates for surgery, with less than or equal to one third of chemotherapy and/or radiotherapy treatment initially scheduled, a life expectancy greater than 3 months, oral intake of food and drinks, adequate cultural level and understanding of the clinical study.

Participants will be randomized in 3 arms:

1. Group A (150mg de DMB equivalent to 2, 8 mg of miraculin glycoprotein + 150g of freeze-dried strawberry).

2. Group B (300 mg of DMB equivalent to 5, 5 mg of the miraculin glycoprotein).

3. Group C (300 mg of strawberry lyophilisate).

Follow up will include 6 individualized visits, to perform the following tests at each visits:

Selection visit

• Nutritional assessment

• Electrogustometry

• Olfactory-gustative test (test strips)
• Taste and smell survey.

1º visit:

• Measurement of blood pressure and heart rate
• Morphofunctional assessment:

o Anthropometry measures (weight, % weight loss, height, BMI, ICA)

o Bioelectrical impedance (BIA): musculoskeletal mass index (MMI), phase angle (FA), extracellular water (EW), intracellular water (IW) and total water (TBW), fat mass (FM), muscle mass (MM), total cell mass, representation phase angle vector (BIVA)

o Dynamometry

o Nutritional ultrasound

o Functionality test (Up and Go Test)

• Olfactory-gustative test (Sniffin'Stick Smell Test)
• Saliva volume.
• Analytic:

o Biochemistry (albumin, prealbumin, retinol-binding protein (RBP), glucose, lipid profile (Total Cholesterol (TC), triglycerides (TG), HDL, LDL), safety parameters (transaminases, urate, creatinine), fat-soluble vitamins (A, D, E), B12, folate, iron metabolism, Zn, Se. Hemogram, lymphocytes, coagulation, hsCRP)

o Stool microbiota and metagenome

o Saliva microbiota and metagenome

o Plasma metabolomes

o Quantitative profile of fatty acids in erythrocytes (enzymatic activity of catalase (CAT), superoxide dismutase (SOD), glutathione-reductase (GR) and glutathione peroxidase (GPOX))

o Plasma cytokine profile (Interleukin (IL) 1β, 4, 6, 8, 10 tumor necrosis factor (TNFα), interferon γ (IFNγ), sIL6R, sTNFR)

o Metabolites in urine

o System status of antioxidant status (hydroxyguanosine and F2-Isoprostanes)

2º visit:

• Anthropometric measures
• Electrogustometry
• Olfactory-gustative test
• Saliva volume
• Taste and smell survey
• Product efficacy satisfaction questionnaire (post-QTx)

3º and 4º visit:

• Morphofunctional assessment:
• Measurement of blood pressure and heart rate,
• Electrogustometry
• Olfactory-gustative test
• Saliva volume
• Taste and smell survey
• Product efficacy satisfaction questionnaire (pre-QTx)
• Analytic:

o Biochemistry

o Stool microbiota and metagenome (v3)

o Saliva microbiota and metagenome

o Plasma metabolomes

o Quantitative profile of fatty acids in erythrocytes

o Plasma cytokine profile

o Metabolites in urine

o System status of antioxidant status

5º visit:

• Morphofunctional assessment:
• Measurement of blood pressure and heart rate,
• Electrogustometry
• Olfactory-gustative test
• Saliva volume
• Taste and smell survey
• Product efficacy satisfaction questionnaire (pre-QTx)
• Analytic:

o Biochemistry

o Stool microbiota and metagenome (v3)

• Saliva microbiota and metagenome
• Plasma metabolomes
• Quantitative profile of fatty acids in erythrocytes
• Plasma cytokine profile
• Metabolites in urine
• System status of antioxidant status

Conditions

Cancer; Dysgeusia; Hypogeusia; Ageusia; Chemotherapy Effect; Malnutrition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

Group A

Pills with 300 mg of DMB equivalent to 5,5 mg of the miraculin glycoprotein

Group Type: EXPERIMENTAL

DMB highest dose

Intervention Type: DIETARY_SUPPLEMENT

Intake of 300 mg of DMB

Group B

Pills with 150 mg of DMB equivalent to 2,8 mg of miraculin glycoprotein + 150g of freeze-dried strawberry

Group Type: EXPERIMENTAL

DMB lowest dose

Intervention Type: DIETARY_SUPPLEMENT

Intake of 150 mg of DMB

Group C

Pills with 300 mg of strawberry lyophilisate

Group Type: PLACEBO_COMPARATOR

Strawberry lyophilisate

Intervention Type: DIETARY_SUPPLEMENT

Intake of 300 mg of strawberry lyophilisate

Interventions

DMB lowest dose

Intake of 150 mg of DMB

Intervention Type: DIETARY_SUPPLEMENT

DMB highest dose

Intake of 300 mg of DMB

Intervention Type: DIETARY_SUPPLEMENT

Strawberry lyophilisate

Intake of 300 mg of strawberry lyophilisate

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Experimental 1; Experimental 2; Placebo comparator

Eligibility Criteria

Inclusion Criteria

• Men and women over 18
• Patients with a weight loss >=5 %
• Patient with malnutrition assessed by Global Leadership Initiative on Malnutrition (GLIM) Criteria
• Patients with taste alterations measured by electrogustometry
• Cancer patients treated with neoadjuvant chemotherapy prior to surgery, chemotherapy or chemo-radiotherapy who are not candidates for surgery.
• Patients with less than or equal to one third of chemotherapy and/or radiotherapy treatment initially scheduled.
• Patients with a life expectancy greater than 3 months.
• Patient with oral intake of food and drinks.
• Adequate cultural level and understanding of the clinical study.
• Agree to voluntarily participate in the study and give their signed written informed consent.

Exclusion Criteria

• Patients who are participating in other clinical trials.
• Patients with a weight loss < 5%
• Patients with a parenteral o enteral nutrition
• Patients diagnosed with poorly controlled Diabetes Mellitus (HbA1 c>8%)
• Patients with uncontrolled high blood pressure.
• Patients with uncontrolled hyper/hypothyroidism.
• Patients with severe digestive toxicity due to treatment with chemo-radiotherapy
• Patients with a life expectancy of less than 3 months.
• Patients diagnosed with severe kidney or liver disease (chronic kidney failure, nephrotic syndrome, cirrhosis).
• Patients with severe dementia, brain metastases, eating behavior disorders, history of serious neurological or psychiatric pathology that may interfere with treatment.
• Patients suffering from alcoholism or substance abuse that may interfere with adherence to treatment.
• Patients with serious gastrointestinal diseases.
• Patients who reject the consumption of DMB.
• Pregnant or lactating women.
• Assessment that, in the clinician's opinion, prevents the patient from participating (severity, etc.)

Withdrawal Criteria:

• Intolerance to the consumption of DMB or Placebo

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Nutrición y Tecnología de los Alimentos

OTHER

Sponsor Role: collaborator

Medicinal Gardens S.L

UNKNOWN

Sponsor Role: collaborator

Instituto de Investigación Hospital Universitario La Paz

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samara Palma-Milla, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto de Investigación Hospital Universitario La Paz

Locations

Bricia LOPEZ PLAZA

Madrid, , Spain

Countries

Spain

References

Lopez-Plaza B, Gil A, Menendez-Rey A, Bensadon-Naeder L, Hummel T, Feliu-Batlle J, Palma-Milla S. 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. Nutrients. 2023 Nov 1;15(21):4639. doi: 10.3390/nu15214639.

Reference Type: RESULT

PMID: 37960292 (View on PubMed)

Alvarez-Mercado AI, Lopez-Plaza B, Plaza-Diaz J, Arcos-Castellanos L, Ruiz-Ojeda FJ, Brandimonte-Hernandez M, Feliu-Batlle J, Hummel T, Palma-Milla S, Gil A. Miraculin Can Contribute to a Reduction in Inflammatory Biomarkers and Cachexia in Malnourished Patients with Cancer and Taste Disorders. Pharmaceuticals (Basel). 2025 Apr 25;18(5):622. doi: 10.3390/ph18050622.

Reference Type: DERIVED

PMID: 40430444 (View on PubMed)

Lopez-Plaza B, Alvarez-Mercado AI, Arcos-Castellanos L, Plaza-Diaz J, Ruiz-Ojeda FJ, Brandimonte-Hernandez M, Feliu-Batlle J, Hummel T, Gil A, Palma-Milla S. Efficacy and Safety of Habitual Consumption of a Food Supplement Containing Miraculin in Malnourished Cancer Patients: The CLINMIR Pilot Study. Nutrients. 2024 Jun 17;16(12):1905. doi: 10.3390/nu16121905.

Reference Type: DERIVED

PMID: 38931260 (View on PubMed)

Other Identifiers

HULP 6164

Identifier Type: -

Identifier Source: org_study_id