Efficacy of Pain Treatment on Depression in Patients With Dementia (DEP-PAIN-DEM)

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

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.

Study Overview

• Status: Completed
• Conditions: Depression; Pain; Dementia
• Intervention / Treatment: Drug: Paracetamol; Drug: Buprenorphine; Drug: Paracetamol placebo; Drug: Buprenorphine placebo

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway
    • University of Bergen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Paracetamol or buprenorphine treatment; 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; Paracetamol granulate supplied by Weifa (Paracet) and 1 g paracetamol tablets produced by Kragerø tablettproduksjon for blinding purposes.; Other Names: Paracet (Weifa); Drug: Buprenorphine; Buprenorphine 5 micrograms/hour and 10 micrograms/hour transdermal system produced by Mundipharma, identical to placebo transdermal system.; Other Names: Norspan (Mundipharma)
Placebo Comparator: Paracetamol placebo or buprenorphine placebo; Paracetamol placebo tablet three times daily or buprenorphine transdermal system placebo every 7 days.	Drug: Paracetamol placebo; Paracetamol placebo tablets produced by Kragerø tablettproduksjon.; Drug: Buprenorphine placebo; Buprenorphine transdermal system placebo produced by Mundipharma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Change in the burden to personnel as measured by NPI-NH subscale	Week 0, week 6 and week 13

Collaborators and Investigators

• Sponsor: University of Bergen
• Investigators: Study Director: Bettina S Husebø, PhD, MD, University of Bergen; Principal Investigator: Elisabeth Flo, PhD, University of Bergen; Principal Investigator: Ane Erdal, PhD candidate, University of Bergen

Publications and helpful links

General Publications

• McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2020 Nov 15;11(11):CD009178. doi: 10.1002/14651858.CD009178.pub4.
• Erdal A, Flo E, Aarsland D, Ballard C, Slettebo DD, Husebo BS. Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM). Drugs Aging. 2018 Jun;35(6):545-558. doi: 10.1007/s40266-018-0546-2.
• Blytt KM, Husebo B, Flo E, Bjorvatn B. Long-Term Pain Treatment Did Not Improve Sleep in Nursing Home Patients with Comorbid Dementia and Depression: A 13-Week Randomized Placebo-Controlled Trial. Front Psychol. 2018 Feb 13;9:134. doi: 10.3389/fpsyg.2018.00134. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): December 21, 2016
• Study Completion (Actual): December 21, 2016

Study Registration Dates

• First Submitted: July 7, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (Estimate): October 17, 2014

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Analgesia; Pain management; Pain measurement; Alzheimer disease; Vascular dementia; Lewy body disease; Depressive symptoms; Analgesics; Pain assessment; Multi-infarct dementia; Frontotemporal lobar degeneration
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mood Disorders; Neurocognitive Disorders; Depression; Depressive Disorder; Dementia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine; Acetaminophen
• Other Study ID Numbers: NFR project nr 221951; 2013-002226-23 (EudraCT Number)