Prospective Cohort Study of Health Complaints

Study Overview
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Brief Summary
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The aim of this study is to evaluate if amalgam removal is associated with improved self-reported health, compared to no amalgam removal. The main target group consists of a group of patients with medically unexplained physical symptoms (MUPS), which they attribute to dental amalgam restorations. The patients should furthermore express the wish to have these amalgam fillings removed. The project is designed as a prospective cohort study, consisting of three groups recruited separately. The main target group will be compared with two comparison groups: one group of patients with MUPS recruited from general practice and one group of healthy study patients, recruited at dental practice. The primary research question is if amalgam removal is associated with improved self-reported health, compared to no amalgam removal, one year after completed amalgam removal.

Detailed Description
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In Norway 5%-8% of the adult population believe that their amalgam fillings have affected their health adversely; and a similar proportion of the adult population has had their amalgam fillings removed for health reasons only. The Norwegian Ministry of Health and Care Services has decided to fund a project comprising experimental treatment (i.e. removal of amalgam fillings) for patients with health complaints which they attribute to dental amalgam. The aim of this study is to evaluate the intervention by measuring health complaints and quality of life before and after amalgam removal and to compare changes over time with relevant patient groups. Amalgam-attributed health complaints are heterogeneous and a variety of symptoms have been attributed to amalgam. Therefore, amalgam related health complaints are difficult to quantify. However, amalgam-attributed health complaints are largely similar to complaints experienced by patients with so called medically unexplained physical symptoms (MUPS). Therefore, in order to operationalize and measure the patient's subjective health complaints, the MUPS criteria and questionnaire will be applied to patients who attribute their health problems to amalgam. Furthermore, this strategy allows for the inclusion of patients suffering from MUPS, however without any attribution to amalgam. This group of patients can serve as a comparison group with a similar symptom load, but no subjective attribution to amalgam. For the interpretation of the study outcome, the natural course of the health complaints in this group is of high importance. Therefore, the project is designed as a prospective cohort study, consisting of three groups recruited separately. The two comparison groups consist of one group of patients with MUPS recruited from general practice and one group of healthy study patients, recruited at dental practice. These study participants are recruited regardless of amalgam status. The main target group consists of a group of patients with medically unexplained physical symptoms, which they attribute to dental amalgam restorations. The patients should furthermore express the wish to have these amalgam fillings removed (amalgam cohort). Patients with amalgam attributed health complaints who suffer from medically explained disease but attribute their diagnosis and course of the disease to amalgam (thus, not included in the amalgam cohort), will be included in a separate case series (amalgam - case series, to be registered as a separate study). Patients in the amalgam cohort will have all amalgam fillings removed according to pre-defined criteria. Amalgam removal will be performed by the patient's regular dentist or another dentist chosen by the patient. After completed removal, patients in the amalgam groups will be examined at a Regional Dental Center of Competence. The costs of amalgam removal will be reimbursed according to pre-defined rules.

Official Title
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Amalgam Removal in Patients With Health Complaints Attributed to Amalgam Restorations: A Prospective Cohort Study

Conditions
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Health Complaints Attributed to Dental Amalgam Restorations

Intervention / Treatment
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* Device: Removal of dental amalgam restorations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (all groups): permanent residents in Norway able to comply with the protocol Amalgam Cohort: Health complaints attributed (by the patient) to dental amalgam restorations duration of the health complaints attributed to amalgam restorations (by the patient) at least 3 months presence of at least one amalgam filling the patient has expressed a wish to have all amalgam fillings removed patient examined by patient's physician and dentist according to guidelines from the Norwegian Directorate of Health diagnosed diseases adequately treated patient's general practitioner/family physician and dentist assess that the patient's general health and dental health most likely will not deteriorate due to participation in the project patient's dentist assess that there are no major risks for dental complications following amalgam removal (e.g. need for root canal treatments or extractions) subjective symptoms without corresponding objective findings after medical examination(s), including symptoms not explained by patient's diagnoses, moderate or severe functional impairment (assessed by the physician) MUPS-cohort: duration of unspecific health complaints at least 3 months subjective symptoms without corresponding objective findings after medical examination(s), including symptoms not explained by patient's diagnoses moderate or severe functional impairment (assessed by the physician) diagnosed diseases adequately treated no attribution to amalgam and no explicit wish to remove amalgam Dental cohort: subjectively healthy without diagnosed chronic disease or prescribed medication Exclusion Criteria (all groups): pregnancy (or planned pregnancy) and lactation life threatening disease patients with ongoing cancers, severe cardiopulmonary, neurological, or psychiatric diseases (assessed by GP)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Amalgam cohort<br>Patients with medically unexplained physical symptoms attributed to dental amalgam restorations which the patient wish to have removed. | Device: Removal of dental amalgam restorations<br>* Patients in the amalgam cohort will have all dental amalgam restorations removed and replaced with other restorative materials used in modern dentistry. Amalgam removal will be performed by the patient's regular dentist or another dentist chosen by the patient.<br>|
| MUPS-cohort<br>Patients with medically unexplained physical symptoms without attribution to amalgam and no explicit wish to remove amalgam. | |
| Dental cohort<br>Healthy comparison group: Subjectively healthy without diagnosed chronic disease or prescribed medication. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-reported health complaints - General index | Primary outcome is the general index from Self-reported health complaints (used by Sjursen et al 2011) at 1 year follow-up after completed amalgam removal. Changes from baseline to 1 year follow-up after amalgam removal of the amalgam cohort will be compared with changes in the MUPS-cohort from baseline to 2 year follow-up. | 1 year follow-up after completed amalgam removal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GBB-24, total score | Change score at 1 and 5 year follow-up | 1 and 5 year follow-up after completed amalgam removal | 
| SF-36 Health Survey | Change score at 1 and 5 year follow-up | 1 and 5 year follow-up after completed amalgam removal | 
| Munich amalgam checklist | Change score at 1 and 5 year follow-up | 1 and 5 year follow-up after completed amalgam removal | 
| Cantril Ladder Scale | Change score at 1 and 5 year follow-up | 1 and 5 year follow-up after completed amalgam removal | 
| Integrative Medicine Outcomes Scale | Change score at 1 and 5 year follow-up | 1 and 5 year follow-up after completed amalgam removal | 
| Diagnostic criteria for BDS | Fulfillment of diagnostic criteria for BDS at baseline and follow-up | 1 and 5 year follow-up after completed amalgam removal | 
| Whiteley index | Change score at 1 and 5 year follow-up | 1 and 5 year follow-up after completed amalgam removal | 
| HADS | Change score at 1 and 5 year follow-up | 1 and 5 year follow-up after completed amalgam removal | 
| Reclassification of symptoms | Reclassification of symptoms from MUPS to symptoms from explained organic disease at follow-up | 1 and 5 year follow-up after completed amalgam removal | 
| Concentration of mercury in plasma | Change from baseline to 1 and 5 year follow-up | 1 year follow-up after completed amalgam removal | 
| Concentration of cytokines in plasma | Change from baseline to 1 and 5 year follow-up | 1 year follow-up after completed amalgam removal | 
| Self-reported health complaints - General index | Change from baseline to 5 year follow-up | 5 year follow-up after completed amalgam removal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amalgam, Mercury, Plasma, Cytokine, Health complaints