Clinical trial NCT01682278: Prospective Cohort Study of Health Complaints
Official title: Amalgam Removal in Patients With Health Complaints Attributed to Amalgam Restorations: A Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Health Complaints Attributed to Dental Amalgam Restorations
Keywords: Health complaints
Amalgam
Mercury
Plasma
Cytokine
Lead sponsor: NORCE Norwegian Research Centre AS
Sponsor class: OTHER
Collaborators: name: University of Bergen
name: National Research Centre of Complementary and Alternative Medicine, Norway
name: University of Witten/Herdecke
First posted: 2012-09-10
Enrollment: 118
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be selected from primary care clinics and dental clinics in Norway.

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Self-reported health complaints - General index
timeFrame: 1 year follow-up after completed amalgam removal
Secondary outcomes:
measure: GBB-24, total score
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: SF-36 Health Survey
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: Munich amalgam checklist
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: Cantril Ladder Scale
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: Integrative Medicine Outcomes Scale
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: Diagnostic criteria for BDS
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: Whiteley index
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: HADS
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: Reclassification of symptoms
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: Concentration of mercury in plasma
timeFrame: 1 year follow-up after completed amalgam removal
measure: Concentration of cytokines in plasma
timeFrame: 1 year follow-up after completed amalgam removal
measure: Self-reported health complaints - General index
timeFrame: 5 year follow-up after completed amalgam removal
Other outcomes:
measure: Health resource use
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: Sick leave
timeFrame: 1 and 5 year follow-up after completed amalgam removal
measure: Costs
timeFrame: 1 and 5 year follow-up after completed amalgam removal
Locations:
city: Bergen
country: Norway
facility: Uni Health
Study officials:
affiliation: NORCE Norwegian Research Centre AS
name: Lars Björkman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bjorkman L, Musial F, Alraek T, Werner EL, Weidenhammer W, Hamre HJ. Removal of dental amalgam restorations in patients with health complaints attributed to amalgam: A prospective cohort study. J Oral Rehabil. 2020 Nov;47(11):1422-1434. doi: 10.1111/joor.13080. Epub 2020 Aug 30.
citation: Bjorkman L, Musial F, Alraek T, Werner EL, Hamre HJ. Mercury, silver and selenium in serum before and after removal of amalgam restorations: results from a prospective cohort study in Norway. Acta Odontol Scand. 2023 May;81(4):298-310. doi: 10.1080/00016357.2022.2143422. Epub 2022 Nov 16.
citation: Lamu AN, Bjorkman L, Hamre HJ, Alraek T, Musial F, Robberstad B. Validity and responsiveness of EQ-5D-5L and SF-6D in patients with health complaints attributed to their amalgam fillings: a prospective cohort study of patients undergoing amalgam removal. Health Qual Life Outcomes. 2021 Apr 17;19(1):125. doi: 10.1186/s12955-021-01762-4.