A Provocation Study Using Biogenic Amines to Show the Efficacy of Oral Diamine Oxidase Supplementation

Study Overview
=================
Brief Summary
-----------------
This study aims to define a provocation test for histamine intolerance (aka. biogenic amine intolerance syndrome) and test the capability of an oral enzyme supplementation to ameliorate this condition.

Detailed Description
-----------------
The clinical picture of the so-called histamine intolerance has been described by various authors since the 1990ies. However, the existence of this multifactorial condition is also being contested due to the lack of both a positive definition and unambiguous diagnostics. Various provocation studies using pure histamine or histamine-containing foods support the existence of the disease pattern, however many questions still remain open. A lack of diamine oxidase (DAO) is considered the etiological cause of the condition. DAO is an enzyme known to degrade a wide array of biogenic amines. The aim of this study is to provoke a response in patients by oral administration of a defined mixture of biogenic amines. By administration of DAO before provocation an attenuation of the symptoms is to be expected.

Official Title
-----------------
A Doubleblind, Placebo-controlled, Cross-over Provocation Study Using Biogenic Amines to Show the Efficacy of Oral Diamine Oxidase (DAOSiN®) Supplementation in Case of DAO Enzyme Deficiency

Conditions
-----------------
Histamine Intolerance

Intervention / Treatment
-----------------
* Dietary Supplement: DAOSiN®/ Placebo & ProvokAmin® Ingestion
* Procedure: Drawing blood, measuring BP & pulse


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Persons suspected of suffering from BAIS (BAIS Score ≥ 50) according the the questionaire used for histamine intolerance so far Exclusion Criteria: pregnancy coronary heart disease labile hypertension bronchial asthma periodical therapy using H1-blockers chirurgical intervention with the GI tract within the previous 3 months participation in a clinical trial within the previous 4 weeks

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DAOSiN®/ Placebo & ProvokAmin® Ingestion<br>A sample of blood is drawn from Patient, blood pressure & pulse are recorded. Patient will ingest 2 capsules of either DAOSiN® or Placebo, followed by 2 tablets of ProvokAmin 20 minutes later. After an additional 40 minutes blood pressure and pulse are recorded and another sample of blood is drawn. Patient is handed a questionaire for self-evaluation to record any symptoms for the following After between 7 and 15 days the whole cycle is repeated switching between active treatment and Placebo. | Dietary Supplement: DAOSiN®/ Placebo & ProvokAmin® Ingestion<br>* Proband is randomly assigned Daosin® or the Placebo before provocation with ProvokAmin®<br>Procedure: Drawing blood, measuring BP & pulse<br>* Taking of a blood sample and recording of blood pressure & pulse<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of biogenic amine symptoms (determined via symptom score) | The primary parameter is the reduction of clinical symptoms caused by the ingestion of biogenic amines by the preventive oral administration of DAOSiN®. A symptom score quantifying the subjective single symptoms is used as measuring parameter. | 24 hrs after start of provocation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serological parameters | These parameters are ascertained: DAO activity and concentration of histamine in serum; blood pressure & pulse measurement before and 30/60/90 min post provocation | Up to 90 min after provocation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
histamine, biogenic amines, diamine oxidase