Efficacy of Pain Treatment on Depression in Patients With Dementia

Study Overview
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Brief Summary
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The purpose of this study is to determine whether pain treatment can reduce symptoms of depression in patients suffering from dementia and depression. Depression is commonly diagnosed in patients with dementia. If the investigators find a reduction in depressive symptoms when pain treatment is applied, this will support the hypothesis that undiagnosed pain may present itself as depression in patients with dementia.

Official Title
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Efficacy of Pain Treatment on Depression in Patients With Dementia. A Randomized Clinical Trial.

Conditions
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Depression, Pain, Dementia

Intervention / Treatment
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* Drug: Paracetamol
* Drug: Buprenorphine
* Drug: Paracetamol placebo
* Drug: Buprenorphine placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients residing in long term nursing home units for at least 4 weeks prior to study Diagnosed with probable or possible dementia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), FAST score > 4 Diagnosed with depression ≥ 4 week duration as measured by CSDD ≥ 8 Written, informed consent provided by the participant (if they have capacity) or assent (if they do not have capacity) and a written proxy informed consent from a legally authorized representative empowered to make health-related decisions for the potential study participant Exclusion Criteria: The patient is contra-indicated to study drugs of pain treatment, in another trial, or had no carer. Participants are ineligible if they are clinical critical (e.g. suicide risk) Clinician responsible for care, or study clinician considers that the patient suffers from any physical condition, which would make participation in the trial distressing or likely to increase suffering Advanced severe medical disease/disorder with expected survival less than 6 months or that could interfere with participation Psychosis or other severe mental disorder prior to dementia diagnosis Severe aggression (≥8) on item 3 of the NPI subscale, with aggression as the predominant symptom Schizophrenia, schizoaffective disorder and bipolar disorder Uncontrolled epilepsy Severe liver impairment Renal failure Severe injury or anaemia (Hb < 8.5 mmol/l), comatose state, current enrolment in another experimental protocol Known allergy or adverse reaction to paracetamol or buprenorphine transdermal patch Advanced severe medical disease with expected survival of less than six months, severe psychiatric or neurological disorder. Patients with diseases that make it impossible to follow the research schedule are excluded

Ages Eligible for Study
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Minimum Age: 60 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Paracetamol or buprenorphine treatment<br>Paracetamol tablets 1 g three times daily or Buprenorphine transdermal system 5 micrograms/hour every 7 days, may be titrated up to 10 micrograms/hour every 7 days if clinically appropriate. | Drug: Paracetamol<br>* Paracetamol granulate supplied by Weifa (Paracet) and 1 g paracetamol tablets produced by Kragerø tablettproduksjon for blinding purposes.<br>* Other names: Paracet (Weifa);Drug: Buprenorphine<br>* Buprenorphine 5 micrograms/hour and 10 micrograms/hour transdermal system produced by Mundipharma, identical to placebo transdermal system.<br>* Other names: Norspan (Mundipharma);|
| Placebo Comparator: Paracetamol placebo or buprenorphine placebo<br>Paracetamol placebo tablet three times daily or buprenorphine transdermal system placebo every 7 days. | Drug: Paracetamol placebo<br>* Paracetamol placebo tablets produced by Kragerø tablettproduksjon.<br>Drug: Buprenorphine placebo<br>* Buprenorphine transdermal system placebo produced by Mundipharma.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Cornell Scale for Depression in Dementia (CSDD) |  | Week -2, week 0, week 6 and week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in actigraphy recorded sleep patterns and circadian rhythm | Actigraph will be used for a period of 1 week before study treatment starts, and in the last week of treatment, on a selection of patients in the placebo group and in the treatment group. | Week -1 to 0 and week 12 to 13 | 
| Change in the Neuropsychiatric Inventory - Nursing Home Version (NPI-NH) |  | Week -1, week 0, week 6 and week 13 | 
| Change in the Mini-Mental State Examination (MMSE) |  | Week -1 and week 13 | 
| Change in the Mobilization- Observation - Behavior - Intensity - Dementia-2 (MOBID-2) Pain Scale |  | Week -1, week 0, week 6 and week 13 | 
| Change in the Numerical Rating Scale (NRS) |  | Week 0, week 6 and week 13 | 
| Change in the Quality of life in late-stage dementia (QUALID) scale |  | Week -1, week 0, week 6 and week 13 | 
| Change in the EuroQoL Quality of Life Scale (EQ-5D) |  | Week -1, week 0, week 6 and week 13 | 
| Adverse events (AE) and serious adverse event (SAE) | Any AE or SAE will be recorded and treated as clinically appropriate throughout the study period. | Weeks 0-13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lewy body disease, Analgesia, Pain measurement, Pain assessment, Pain management, Analgesics, Depressive symptoms, Alzheimer disease, Vascular dementia, Multi-infarct dementia, Frontotemporal lobar degeneration