Fibromyalgia Treatment With Enzyme DAO

Sponsor

Centros de Investigación de Nutrición y Salud (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05389761

Collaborator

AB Biotek (Industry)

100

Enrollment

Location

Arms

7.2

Anticipated Duration (Months)

13.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Fibromyalgia is a complex and common chronic pain disorder that affects 12 million Europeans. Fibromyalgia causes persistent widespread pain in muscles, tendons, ligaments, and joints, as well as widespread tenderness to touch and the presence of extreme fatigue and weakness.

Histamine is a molecule derived from an essential amino acid, histidine. It is stored in mast cells and basophils and is excreted through the intestine, being degraded as it passes through the intestinal mucosa by the enzyme Diamine Oxidase (DAO), which is found in this area. If there is any alteration in its metabolism and normal concentrations of histamine in the blood (50-70 mg/l) are not maintained, the free circulation of this amine in high concentrations triggers undesired effects, such as migraine, fibromyalgia, asthenia and atopy.

DAO deficiency is an alteration in the metabolism of dietary histamine that occurs when there is little activity of the DAO enzyme. The low activity of the enzyme causes that a concentration considered normal of histamine from food cannot be metabolized and a transepithelial penetration of exogenous histamine occurs. In this way, histamine passes into the bloodstream, increasing its plasma concentration and once located freely in the blood, it is distributed throughout different parts of the body, producing adverse effects.

One of the factors that causes DAO deficiency is genetics. The genetic sequence of DAO is found in a fragment located on chromosome 7 (7q34-q36) of the human genome. There are 85 single nucleotide variants (SNPs) located and identified in the human DAO gene (AOC1). Seven of these SNPs produce amino acid substitution, being candidates to cause alterations in the metabolic capacity of the enzyme.

Since histamine accumulation can trigger fibromyalgia, and the enzyme DAO has been shown to degrade histamine, oral supplementation with DAO food supplements, prepared from pig kidney, is suggested as a treatment for fibromyalgia.

The objective of this study is to analyze whether DAO enzyme supplementation reduces the characteristic symptoms of fibromyalgia. In addition, the prevalence of DAO deficiency in women with fibromyalgia will be identified by genetic analysis of DAO deficiency from a saliva sample. It will also be evaluated if patients require a lower intake of analgesics after supplementation with the enzyme DAO.

Condition or Disease	Intervention/Treatment	Phase
Fibromyalgia	Dietary Supplement: fibroDAO® Dietary Supplement: Placebo	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Supportive Care

Official Title:

Evaluation of the Efficacy of Fibromyalgia Treatment With Enzyme DAO (Diamine-oxidase)

Actual Study Start Date :

Feb 22, 2022

Actual Primary Completion Date :

May 5, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enzyme DAO administration DAO enzyme supplementation for 6 months	Dietary Supplement: fibroDAO® One DAO enzyme capsule is taken with water 20 minutes before each meal, 3 times a day. DAO enzyme capsules contains 0.3 mg DAO enzyme divided into 2 white/beige tablets (each gastro-resistant tablet contains 0.15 mg DAO enzyme) and 80 mg magnesium divided into 2 lilac tablets (each immediate-release tablet contains 40 mg of Mg).
Placebo Comparator: Placebo administration Placebo supplementation for 6 months	Dietary Supplement: Placebo One placebo capsule is taken with water 20 minutes before each meal, 3 times a day. Placebo capsules consist of microcrystalline cellulose and gelatin capsules with the same shape, size and colour as the DAO enzyme.

Arm

Intervention/Treatment

Experimental: Enzyme DAO administration

DAO enzyme supplementation for 6 months

Dietary Supplement: fibroDAO®

One DAO enzyme capsule is taken with water 20 minutes before each meal, 3 times a day. DAO enzyme capsules contains 0.3 mg DAO enzyme divided into 2 white/beige tablets (each gastro-resistant tablet contains 0.15 mg DAO enzyme) and 80 mg magnesium divided into 2 lilac tablets (each immediate-release tablet contains 40 mg of Mg).

Placebo Comparator: Placebo administration

Placebo supplementation for 6 months

Dietary Supplement: Placebo

One placebo capsule is taken with water 20 minutes before each meal, 3 times a day. Placebo capsules consist of microcrystalline cellulose and gelatin capsules with the same shape, size and colour as the DAO enzyme.

Outcome Measures

Primary Outcome Measures

Patient status, progress and outcomes [Baseline, 2 months and 6 months]
Change from baseline in fibromyalgia status on the Fibromyalgia Impact Questionnaire (FIQ). The FIQ has10 items. Each item has a maximum possible score of 10. The maximum possible score is 100. A higher score indicates a greater impact of the syndrome.
Sleep quality [Baseline, 2 months and 6 months]
Change from baseline in sleep quality on the Pittsburgh Sleep Quality Index (PSQI). The PSQI contains 19 questions scored from 0 (no difficulty) to 3 (severe difficulty). The overall score is from 0 to 21. Higher scores indicate poorer sleep quality.
Pain experience [Baseline, 2 months and 6 months]
Change from baseline in pain on the Pain Catastrophizing Scale (PCS). The PCS contains 13 items that are rated on 5-point Likert scales, from 0 (not at all) to 4 (all the time). The minimum total score is 0 and the maximum is 52. A higher score indicates a higher level of catastrophizing.
Extent and severity of eczema [Baseline, 2 months and 6 months]
Change from baseline in eczema on the SCORing Atopic Dermatitis (SCORAD). The extension can be scored from 0 to 100, intensity from 0 to 18, and subjective symptoms from 0 to 20. The final score is achieved using the formula A / 5 + 7B / 2 + C.
Impact of headache [Baseline, 2 months and 6 months]
Change from baseline in headache on the Headache Impact Test-6 (HIT-6). HIT-6 has six questions, each with five response categories: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score is obtained by adding the responses to the six items. Scores ≥ 60 indicate severe life impact, 56-59 substantial life impact, 50-55 some life impact, and ≤ 49 minimal or no life impact.

Secondary Outcome Measures

Prevalence of DAO deficiency [Baseline]
Genetic analysis of DAO deficiency
Analgesic intake [Baseline, 2 months and 6 months]
Changes in analgesics intake. An ad-hoc questionnaire is used, where patients are asked to indicate the analgesics they take.

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 59 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female
Age between 30 and 59 years (included)
Diagnosis of fibromyalgia
Must sign an informed consent
Able to follow-up at 2 and 6 months

Exclusion Criteria:

Pregnant or possibly pregnant
Patients with change of pharmacological treatment in the last 3 months
Patients with DAO enzyme treatment
Patients diagnosed with other severe diseases (i.e. cancer, cardiovascular disease, autoimmune disease or metabolic disease)
Patients with multiple chemical sensitivity