Histamine Intolerance
Conditions
Keywords
diamine oxidase, histamine intolerance, safety, tolerability, pea sprout, diamine oxidase supplementation
Brief summary
The present study was conducted to assess the safety and tolerability of five ascending doses of plant-based DAO enzyme supplement in subjects with symptoms of histamine intolerance.
Interventions
DIETARY_SUPPLEMENTDiamino Oxidase
The investigational product is a dehydrated power of DAO enzyme from green pea (Pisum sativum L.) sprouts (adiDAO®Veg, DR Healthcare, S.L.U., Barcelona, Spain), with an enzymatic activity \> 298 mU/g (\> 14,500 kHDU/g).
Sponsors
Hospital Clinic of Barcelona
AB Biotek
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
After signing the informed consent, participants start taking the standard dose of 4.2 mg of adiDAO®Veg three times a day for a period of 2 weeks (phase 1). If the measured DAO enzyme activity levels remain unnormalized, supplementation is continued for a further 2 weeks doubling the dose (8.4 mg) (phase 2), and repeating the process of doubling doses (16.8 mg) (phase 3), 33.6 mg (phase 4), and 67.2 mg (phase 5).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recent history of 2 or more symptoms associated to histamine intolerance. * Altered activity of plasmatic DAO enzyme and/or at least one genetic variants linked to DAO deficiency (rs10156191, rs1049742, rs1049793, rs2052129). * Not having started a dietary intervention (low histamine diet or DAO supplementation) before the start of this study.
Exclusion criteria
* Treatment with low-histamine diet and/or dietary DAO enzyme supplementation prior to the study. * Pharmacological treatment with antibiotics or probiotic supplements within the last month prior to enrollment. * Breast-feeding or pregnant women. * Inability to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events (AEs) | At day 14, day 28, day 42, day 56 and day 70. | Number of participants with treatment-related adverse events (AEs) experienced during the supplementation, assessed through a questionnaire. |
| Type of adverse effects (AEs) | At day 14, day 28, day 42, day 56 and day 70. | Symptoms of adverse effects (AEs) experienced during the supplementation, assessed through a questionnaire including the different body systems: gastrointestinal, CNS, respiratory, dermatological). |
| DAO enzymatic activity in serum using a radioextraction immunoassay | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | DAO enzymatic activity in serum (mU/mL) using a radioextraction immunoassay (REA-3H, Laboratorio Echevarne, Barcelona, Spain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glycemia | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Glycemia for safety assessment |
| HbA1c | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | HbA1c for safety assessment |
| Ionogram | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Ionogram for safety assessment |
| Lipid profile | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Lipid profile |
| C-reactive protein | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | C-reactive protein for safety assessment |
| Interleukin-6 | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Interleukin-6 for safety assessment |
| Proteinuria | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Proteinuria from urine sample |
| Urine sediment | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Urine sediment from urine sample for safety assessment |
| Gastrointestinal symptoms through Rome IV criteria | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported Gastrointestinal symptoms: Rome IV criteria |
| Gastrointestinal symptoms through Bristol Stool Scale | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported Gastrointestinal symptoms: Bristol Stool Scale. Score goes from Type 1 to Type 7. Higher and lower scores mean worse outcome. Middle scores (Type 3-4) are considered normal/healthy stool consistency. |
| Gastrointestinal symptoms through Gastrointestinal Quality of Life Index (GIQLI) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported Gastrointestinal symptoms: Gastrointestinal Quality of Life Index (GIQLI). Score goes from 0 to 144. Higher scores indicate a better outcome. |
| Headaches symptoms through MIDAS questionnaire | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported Headaches symptoms through Migraine Disability Assessment Questionnaire (MIDAS) questionnaire. Score goes from 0 to \>21 points. Higher scores indicate a worse outcome. |
| Headaches symptoms through HIT-6 questionnaire | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported Headaches symptoms through Headache Impact Test-6 (HIT-6) questionnaire. Score goes from 36 to 78. Higher scores indicate a worse outcome. |
| Respiratory symptoms through SNOT-22 questionnaire | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported respiratory symptoms through Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire. Score goes from 0 to 110. Higher scores indicate a worse outcome. |
| Respiratory symptoms through Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Score goes from 0 to 6. Higher scores indicate a worse outcome. | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported respiratory symptoms through Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) |
| Dermatological symptoms through SCORAD index | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported dermatological symptoms through SCORing Atopic Dermatitis (SCORAD) index. Score goes from 0 to 103. Higher scores indicate a worse outcome. |
| Dermatological symptoms through Itch Severity Scale (ISS) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported dermatological symptoms through Itch Severity Scale. Score goes from 0 to 21. Higher scores indicate a worse outcome |
| Dermatological symptoms through Dermatology Life Quality Index (DLQI) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported dermatological symptoms through Dermatology Life Quality Index (DLQI). Score goes from 0 to 20. Higher scores indicate worse outcomes. |
| Short-Form Health Survey (SF-36) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Self-reported Short-Form Health Survey (SF-36) Quality of Life. Score goes from 0 to 100. Higher scores indicate a better outcome. |
| Creatinine (mg/dL) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Creatinine (mg/dL) to assess renal function |
| Glomerular filtration rate (mL/min/1.73m2) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Glomerular filtration rate (mL/min/1.73m2) to assess renal function |
| Uric acid (mg/dL) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Uric acid (mg/dL) to assess renal function |
| Albuminuria (mg/L) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Albuminuria (mg/L) to assess renal function |
| Albumin/creatinine ratio | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Albumin (mg/L)/creatinine (mg/dL) ratio; to assess renal function |
| Urine (mg/g) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Urine (mg/g) ratio; to assess renal function |
| Urinary pH | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Urinary pH to assess renal function |
| Urine specific gravity (g/mL) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Urine specific gravity (g/mL) to assess renal function |
| Aspartate Aminotransferase, ASAT (U/L) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Aspartate Aminotransferase, ASAT (U/L) to assess hepatic function |
| Alanine Aminotransferase, ALAT (U/L) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Alanine Aminotransferase, ALAT (U/L) to assess hepatic function |
| Gamma-Glutamyl Transferase, GGT (U/L) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Gamma-Glutamyl Transferase, GGT (U/L) to assess hepatic function |
| Total Bilirubin (mg/dL) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Total Bilirubin (mg/dL) to assess hepatic function |
| Alkaline Phosphatase (U/L) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Alkaline Phosphatase (U/L) to assess hepatic function |
| Hemogram | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Hemogram |
| Total Proteins (g/L) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Total Proteins (g/L) to assess hepatic function |
| Albumin (g/L) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Albumin (g/L) to assess hepatic function |
| Lactate Dehydrogenase (U/L) | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Lactate Dehydrogenase (U/L) to assess hepatic function |
| Dietary habits | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Dietary habits assessed through a dietary weekly record |
| Histamine in 24h urine | At baseline or day 1, day 14, day 28, day 42, day 56 and day 70. | Histamine in 24h urine |
Countries
Spain
Outcome results
None listed