Clinical trial NCT05486260: Effect of Dried Miracle Berry on the Olfactory-gustative Perception in Malnourished Cancer Patients
Official title: Effect of Regular Consumption of Dried Miracle Berry (DMB) on Taste Perception and Nutritional Status in Malnourished Cancer Patients: A Triple-Blind, Randomized, Placebo-Controlled Clinical Trial. CLINMIR Pilot Protocol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer
Dysgeusia
Hypogeusia
Ageusia
Chemotherapy Effect
Malnutrition
Lead sponsor: Instituto de Investigación Hospital Universitario La Paz
Sponsor class: OTHER
Collaborators: name: Instituto de Nutrición y Tecnología de los Alimentos
name: Medicinal Gardens S.L
First posted: 2022-08-03
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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

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

Primary outcomes:
measure: Electrogustometry
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Sniffing Stick Smell Test
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Strips' Test
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Taste and Smell Survey
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
Secondary outcomes:
measure: Weight (kg)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Waist circumference (cm)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Body Mass Index (kg/m2)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Manual dynamometry
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Muscle ultrasound
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Up and go test
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Saliva volume (mL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Albumin serum concentration (g/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Prealbumin serum concentration (mg/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Glucose serum concentration (mg/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Total Cholesterol serum concentration (mg/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Triglycerides serum concentration (mg/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: LDL-cholesterol serum concentration (mg/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: HDL-cholesterol serum concentration (mg/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: RCP-us serum concentration (mg/L)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Vitamin A serum concentration (μg/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Vitamin D serum concentration (ng/mL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Vitamin E serum concentration (alfa-tocopherol, μg/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Vitamin B12 serum concentration (pg/mL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Folic acid serum concentration (ng/mL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Iron serum concentration (μg/dL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Zinc serum concentration (μg/mL)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Selenium serum concentration (μg/L)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Plasma cytokine concentration
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Saliva microbiota
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Saliva metagenomics
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Faeces microbiota
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Faeces metagenomics
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Plasma metabolomics
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Quantitative profile of fatty acids in erythrocytes
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Concentration of 8-iso-PGF2α in urine
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Concentration of 8-hydroxy-2'-deoxyguanosine in urine
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Total antioxidant capacity (TAC) of plasma
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Determination of oxidized and reduced glutathione in erythrocytes
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Enzyme activity of the antioxidant defense system in erythrocytes
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: CAT catalase activity (EC 1.11.1.6)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: SOD superoxide dismutase activity (EC 1.5.1.1)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Glutathione Reductase Activity GR (EC 1.6.4.2)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: GPOX glutathione peroxidase activity (EC 1.11.1.9)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: 72 hour food record questionnaire
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Food Frequency Consumption Questionnaire (PREDIMED)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: International Physical Activity Questionnaire (IPAQ)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Quality of Life Questionnaire (EORTIC QLQ-C30)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Product Efficacy Satisfaction Questionnaire
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (3 months after chemotherapy)
measure: Fat mass (%)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Muscle mass (%)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Extracellular water(%)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Intracellular water (%)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Total Body Water (%)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Phase angle (º)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
measure: Body Cell Mass (%)
timeFrame: Before chemotherapy, After therapy (3-4 days), Follow up (1 month, 2 months and 3 months after chemotherapy)
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Bricia LOPEZ PLAZA
Study officials:
affiliation: Instituto de Investigación Hospital Universitario La Paz
name: Samara Palma-Milla, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.