Clinical trial NCT01021696: Pain in Patients With Dementia and Behavioural Disturbances
Official title: The Impact of Pain on Behavioural Disturbances in Patients With Moderate and Severe Dementia. A Cluster Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Dementia
Pain
Agitation
Keywords: Dementia
Nursing home
Pain treatment
Pain assessment
Agitation
Lead sponsor: University of Bergen
Sponsor class: OTHER
Collaborators: name: The Research Council of Norway
First posted: 2009-11-30
Enrollment: 352
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In nursing homes (NHs) 80% of the patients have dementia, between 60%-80% exhibit behavioural disturbances (BPSD), and more than 60% have pain. Both pain and BPSD is more common in those with severe dementia. Since older persons with dementia have less communicative skills, suffer from more pain and exhibit more agitation, pain may be a contributing factor in these patients. More than 40% of patients with BPSD are treated with neuroleptics despite described side-effects. There is an urgent need to investigate the impact of individual pain management on BPSD in patients with dementia.

It was hypothesized that

* pain increase BPSD in patients with dementia
* individual pain treatment decrease BPSD in patients with dementia

Detailed description: We intend to conduct an eight weeks, multi-centre, rater-blinded, cluster randomized, and parallel-group trial, with follow up after four weeks. We will choose cluster randomizing by practical reasons. 920 NH patients were screened and 352 patients with moderate or severe dementia and BPSD were included. The treatment period is 8 weeks, with further follow after four weeks.

The primary outcome measure will be reduction in aggression and agitation as well as other items which are measured by means of CMAI (Cohen Mansfield Agitation Inventory). Secondary outcome are reduction in NPI-NH-subscale agitation/aggression and other items which are measured by the Neuropsychiatric Inventory, Nursing Home Version (NPI-NH). Further, we want to evaluate the concomitant use of acute medication. Additionally, Activities of Daily Living function (ADL) and MIni Mental State Examination (MMSE) will be used as secondary outcome measure.

Pain in patients with dementia will be assessed and followed by the MOBID-2 Pain Scale (secondary outcome measure). MOBID-2 Pain Scale is a staff-administered behavioural instrument for assessment pain in older persons with dementia with god validity and reliability (Husebo 2008, 2009). MOBID-2 is based on patient's pain behaviour in connection with standardised, guided movements of different body part, and pain behaviour related to internal organs, head and skin. Additionally, pain will be registered by pain diagnoses, -etiology, and -duration. The MOBID-2 score is derived from caregiver in a clinical bedside situation during morning care.

Adverse events will be recorded and evaluated throughout the study as the primary assessment of safety and tolerability.

Inclusion criteria: Patients of either gender, 60 years of age or older, living in a nursing home (NH) diagnosed moderate or severe dementia measured by the Functional Assessment Staging (FAST) and MMSE, and BPSD in form of agitation / aggression as measured by subscale of NPI-NH and CMAI.

Exclusion criteria: Patients without cognitive impairment and without BPSD. Patients with hepatic or renal failure or diseases that make it impossible to follow the study schedule.

Eligibility criteria: Inclusion Criteria:

* Aged 65 and older
* Residing in the NHs for at least 4 weeks
* Dementia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (American Psychiatric Association 1994), FAST score \> 4 (Hughes 1982).
* Clinically relevant BPSD, operationally defined as CMAI score ≥ 39 or higher or/and at least one week history of agitation or aggression (Koss 1997).
* 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:

* 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, as measured by or equivalent to an estimated creatinine clearance of \< 50mL/min/1.73m,
* Severe injury or anaemia (Hb \< 8.5 mmol/l), comatose state, current enrolment in another experimental protocol.
* Known allergy or adverse reaction to Paracetamol, Morphine ret, Buprenorphine plaster or pregabalin

Primary outcomes:
measure: Cohen-Mansfield Agitation Inventory - long form (CMAI)
timeFrame: CMAI will be used during the screening/inclusion process, at week 2, 4, 8, and 12.
Secondary outcomes:
measure: Neuropsychiatric Inventory - Nursing Home Version (NPI-NH)
timeFrame: NPI will be used during the inclusion process, at week 2, 4, 8, and 12.
measure: Activity of Daily Living function (ADL)
timeFrame: ADL assessment will be used during clinical investigation related to the inclusion prosess and at week 8
measure: Mini Mental State Examination
timeFrame: Screening/clinical investigation and week 8
measure: Mobilisation-Observation-Behavior-Intensity-Dementia-2 (MOBID-2) Pain Scale
timeFrame: Screening/clinical investigation, week 2,4,8,12
measure: Functional Assessment Staging (FAST)
timeFrame: Screening and week 8
measure: Adverse events (AE) and serious adverse event (SAE)
timeFrame: week 2,4,8
Other outcomes:
Locations:
city: Knarvik
country: Norway
facility: Knarvik Nursing Home
state: Horadland
city: Aastveit
country: Norway
facility: Aastveit Nursing Home
state: Hordaland
city: Bergen
country: Norway
facility: Dormkirkehjemmet
state: Hordaland
city: Bergen
country: Norway
facility: Fantoft Omsorgssenter
state: Hordaland
city: Bergen
country: Norway
facility: Bergen Red Cross Nursing Home
state: Hordaland
city: Bergen
country: Norway
facility: Solsletten Sykehjem
state: Hordaland
city: Bergen
country: Norway
facility: Mildeheimen
state: Hordaland
city: Bergen
country: Norway
facility: Søreide Nursing Home
state: Hordaland
city: Isdalsto
country: Norway
facility: Lindas bu- og servicecentre
state: Hordaland
city: Isdalsto
country: Norway
facility: Saata bu og servicecentre
state: Hordaland
city: Laksevag
country: Norway
facility: Lyngbøtunet Nursing Home
state: Hordaland
city: Nesttun
country: Norway
facility: Odinsvei Nursing Home
state: Hordaland
city: Nesttun
country: Norway
facility: Ovsttunheimen
state: Hordaland
city: Hafrsfjord
country: Norway
facility: Slaathaug Nursing Home
state: Rogaland
city: Sandnes
country: Norway
facility: Rovik Nursing Home
state: Rogaland
city: Sola
country: Norway
facility: Sola Nursing Home
state: Rogaland
city: Stavanger
country: Norway
facility: Blidensol Nursing Home
state: Rogaland
city: Stavanger
country: Norway
facility: Tasta Nursing Home
state: Rogaland
Study officials:
affiliation: University of Bergen, Norway
name: Rolv Terje Lie, PhD
role: STUDY_DIRECTOR
affiliation: University of Bergen, Norway
name: Bettina S. Husebo, MD, PhD
role: STUDY_CHAIR
affiliation: University of Bergen, Norway
name: Dag Aarsland, MD, Phd
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College London
name: Clive Ballard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Husebo BS. [Pain assessment in dementia]. Tidsskr Nor Laegeforen. 2009 Oct 8;129(19):1996-8. doi: 10.4045/tidsskr.08.0660. Norwegian.
citation: Husebo BS, Strand LI, Moe-Nilssen R, Husebo SB, Ljunggren AE. Pain behaviour and pain intensity in older persons with severe dementia: reliability of the MOBID Pain Scale by video uptake. Scand J Caring Sci. 2009 Mar;23(1):180-9. doi: 10.1111/j.1471-6712.2008.00606.x. Epub 2009 Jan 20.
citation: Husebo BS, Strand LI, Moe-Nilssen R, Borgehusebo S, Aarsland D, Ljunggren AE. Who suffers most? Dementia and pain in nursing home patients: a cross-sectional study. J Am Med Dir Assoc. 2008 Jul;9(6):427-33. doi: 10.1016/j.jamda.2008.03.001. Epub 2008 Jun 2.
citation: Husebo BS, Strand LI, Moe-Nilssen R, Husebo SB, Snow AL, Ljunggren AE. Mobilization-Observation-Behavior-Intensity-Dementia Pain Scale (MOBID): development and validation of a nurse-administered pain assessment tool for use in dementia. J Pain Symptom Manage. 2007 Jul;34(1):67-80. doi: 10.1016/j.jpainsymman.2006.10.016. Epub 2007 May 23.
citation: Griffioen C, Husebo BS, Flo E, Caljouw MAA, Achterberg WP. Opioid Prescription Use in Nursing Home Residents with Advanced Dementia. Pain Med. 2019 Jan 1;20(1):50-57. doi: 10.1093/pm/pnx268.
citation: Aasmul I, Husebo BS, Flo E. Staff Distress Improves by Treating Pain in Nursing Home Patients With Dementia: Results From a Cluster-Randomized Controlled Trial. J Pain Symptom Manage. 2016 Dec;52(6):795-805. doi: 10.1016/j.jpainsymman.2016.07.004. Epub 2016 Aug 12.
citation: Habiger TF, Flo E, Achterberg WP, Husebo BS. The Interactive Relationship between Pain, Psychosis, and Agitation in People with Dementia: Results from a Cluster-Randomised Clinical Trial. Behav Neurol. 2016;2016:7036415. doi: 10.1155/2016/7036415. Epub 2016 May 9.
citation: Husebo BS, Ballard C, Fritze F, Sandvik RK, Aarsland D. Efficacy of pain treatment on mood syndrome in patients with dementia: a randomized clinical trial. Int J Geriatr Psychiatry. 2014 Aug;29(8):828-36. doi: 10.1002/gps.4063. Epub 2013 Dec 19.
citation: Husebo BS, Ballard C, Cohen-Mansfield J, Seifert R, Aarsland D. The response of agitated behavior to pain management in persons with dementia. Am J Geriatr Psychiatry. 2014 Jul;22(7):708-17. doi: 10.1016/j.jagp.2012.12.006. Epub 2013 Apr 20.
citation: Husebo BS, Ballard C, Sandvik R, Nilsen OB, Aarsland D. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ. 2011 Jul 15;343:d4065. doi: 10.1136/bmj.d4065.