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Pain in Patients With Dementia and Behavioural Disturbances

This study has been completed.
Sponsor:
Collaborator:
The Research Council of Norway
Information provided by:
University of Bergen
ClinicalTrials.gov Identifier:
NCT01021696
First received: November 27, 2009
Last updated: August 9, 2011
Last verified: November 2010
  Purpose

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

Condition Intervention Phase
Dementia
Pain
Agitation
Drug: Paracetamol
Drug: Morphine
Drug: Buprenorphine plaster
Drug: Pregabalin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Impact of Pain on Behavioural Disturbances in Patients With Moderate and Severe Dementia. A Cluster Randomized Trial

Resource links provided by NLM:


Further study details as provided by University of Bergen:

Primary Outcome Measures:
  • Cohen-Mansfield Agitation Inventory - long form (CMAI) [ Time Frame: CMAI will be used during the screening/inclusion process, at week 2, 4, 8, and 12. ] [ Designated as safety issue: No ]
    CMAI has 29-item (max. score 203) to assess agitated behaviours in NH-patients. A six-point rating scale assesses the frequency with which patients manifest BPSD evaluating 29 agitated behaviours, ranging from never, less than once a week, but still occurring, once or twice a week, several times a week, once or twice a day, several times a day or several times an hour. Items are presented in four factors: I Aggressive behaviour; II Physical non-aggressive behaviour; III Verbally agitated behavior, IV hiding and hoarding. Ratings are based on face-to-face interviews with caregivers.


Secondary Outcome Measures:
  • Neuropsychiatric Inventory - Nursing Home Version (NPI-NH) [ Time Frame: NPI will be used during the inclusion process, at week 2, 4, 8, and 12. ] [ Designated as safety issue: No ]
    NPI is a caregiver based interview (10 min.), assessing 10 BPSD and 2 neurovegetative areas with total score and subscales for: delusion, hallucination, agitation, depression, anxiety, disinhibition apathy, irritability, aberrant motor activity, sleep, appetite. Frequency, severity, and caregiver's distress are measured. The NH-version will be used, recently validated in Norwegian (AGS Panel 1998). A higher score reflects increased frequency and severity of the disturbances.

  • Activity of Daily Living function (ADL) [ Time Frame: ADL assessment will be used during clinical investigation related to the inclusion prosess and at week 8 ] [ Designated as safety issue: No ]
    ADL assess physical function. Rating includes activities like feeding, moving, personal toilet, and dressing higher values indicating higher levels of activities of daily functioning and independency (Sheikh 1979). The scale includes 10 items (0-20 score). The ADL score is derived from caregiver interview. Administration of the ADL takes approximately 5 minutes.

  • Mini Mental State Examination [ Time Frame: Screening/clinical investigation and week 8 ] [ Designated as safety issue: No ]
    The MMSE is a 30-point mental status examination scale that enables cut-off differentiation for levels of severity of cognitive impairment (Folstein 1975). Cut point for moderate dementia: <20. The question consist of several orientation question (10 points), registration and recall task (6), attention task (5), three stage command (3), two naming task (2), repetition task (1), reading comprehension task (1), written sentence (1), and a visual construction (1). The test takes 15 minutes to administer and the patient is asked the questions directly by the examiner.

  • Mobilisation-Observation-Behavior-Intensity-Dementia-2 (MOBID-2) Pain Scale [ Time Frame: Screening/clinical investigation, week 2,4,8,12 ] [ Designated as safety issue: No ]
    MOBID-2 Pain Scale is a staff-administered behavioural instrument for assessment pain in older persons with dementia (Husebo 2008a). 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. Administration of the MOBID-2 takes approximately 5 minutes.

  • Functional Assessment Staging (FAST) [ Time Frame: Screening and week 8 ] [ Designated as safety issue: No ]
    FAST describes a continuum of seven stages and sub stages from normality to most severe dementia (Hughes 1982). Moderate to severe dementia is consistent with Fast stage of 5 or 6 or 7. Stage 5 is defined as moderately severe cognitive decline, with deficient performance in activities of daily living such as choosing proper clothing and maintaining hygiene. Stage 6 is defined as severe cognitive decline with incontinence and decreased ability to clothe, bathe, toilet oneself, severely limited speech, vocabulary, emotional expression. FAST score is derived from caregiver interview (5 min).

  • Adverse events (AE) and serious adverse event (SAE) [ Time Frame: week 2,4,8 ] [ Designated as safety issue: Yes ]
    Safety and tolerability assessments will consist of monitoring and recording all adverse events (AE) and serious adverse events (SAE) and the regular monitoring of vital signs (BP, puls); AE and SAE registration and report is related to each patient, each medication each centre with reportation to the Norwegian Medicines Agency (study code EUDRACTNR. 2008-007490-20).


Enrollment: 352
Study Start Date: November 2009
Study Completion Date: October 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Treatment as usual
Control group
Active Comparator: Paracetamol
Intervention group
Drug: Paracetamol
Paracetamol Max. dose: 3g/d
Other Name: Individual pain treatment
Active Comparator: Morphine
Intervention group, individual pain treatment
Drug: Morphine
Morphine ret. Tab. 5mgx2/d; max. dose:10mgx2/d
Other Name: Individual pain treatment
Active Comparator: Buprenorphine plaster
Intervention group, individual pain treatment
Drug: Buprenorphine plaster
5ųg/h, change each 7.day; max. dose: 10ųg/h
Other Name: Individual pain treatment
Active Comparator: Pregabalin
Intervention group, individual pain treatment
Drug: Pregabalin
25mgx1/d; max 300mg/d
Other Name: individual pain treatment

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

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01021696

Locations
Norway
Knarvik Nursing Home
Knarvik, Horadland, Norway, 5914
Aastveit Nursing Home
Aastveit, Hordaland, Norway
Bergen Red Cross Nursing Home
Bergen, Hordaland, Norway, 5035
Dormkirkehjemmet
Bergen, Hordaland, Norway, 5018
Fantoft Omsorgssenter
Bergen, Hordaland, Norway, 5020
Mildeheimen
Bergen, Hordaland, Norway, 5259
Solsletten Sykehjem
Bergen, Hordaland, Norway, 5164
Søreide Nursing Home
Bergen, Hordaland, Norway
Saata bu og servicecentre
Isdalsto, Hordaland, Norway, 5914
Lindas bu- og servicecentre
Isdalsto, Hordaland, Norway, 5914
Lyngbøtunet Nursing Home
Laksevag, Hordaland, Norway, 5164
Ovsttunheimen
Nesttun, Hordaland, Norway, 5223
Odinsvei Nursing Home
Nesttun, Hordaland, Norway, 5222
Slaathaug Nursing Home
Hafrsfjord, Rogaland, Norway, 4042
Rovik Nursing Home
Sandnes, Rogaland, Norway, 4319
Sola Nursing Home
Sola, Rogaland, Norway, 4097
Blidensol Nursing Home
Stavanger, Rogaland, Norway
Tasta Nursing Home
Stavanger, Rogaland, Norway
Sponsors and Collaborators
University of Bergen
The Research Council of Norway
Investigators
Study Director: Rolv Terje Lie, PhD University of Bergen, Norway
Study Chair: Bettina S. Husebo, MD, PhD University of Bergen, Norway
Principal Investigator: Dag Aarsland, MD, Phd University of Bergen, Norway
Principal Investigator: Clive Ballard, MD, PhD King's College London
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bettina Sandgathe Husebo, Department of Public Health and Primary Health Care, University of Bergen
ClinicalTrials.gov Identifier: NCT01021696     History of Changes
Other Study ID Numbers: 2008-007490-20
Study First Received: November 27, 2009
Last Updated: August 9, 2011
Health Authority: Norway: Data Protection Authority
Norway: Directorate of Health
Norway: Ethics Committee
Norway: Norwegian Medicines Agency
Norway: Norwegian Social Science Data Services

Keywords provided by University of Bergen:
Dementia
Nursing home
Pain treatment
Pain assessment
Agitation

Additional relevant MeSH terms:
Dementia
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Acetaminophen
Buprenorphine
Morphine
Pregabalin
Analgesics
Analgesics, Non-Narcotic
Analgesics, Opioid
Anticonvulsants
Antipyretics
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Narcotic Antagonists
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014