Clinical trial NCT00385684: Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
Official title: Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alzheimer Disease
Dementia
Dementia, Vascular
Pain
Keywords: Agitation
Alzheimer Disease
Analgesics
Dementia
Narcotics
Opioid
Pain
Palliative Care
Psychomotor
Suffering, Physical
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2006-10-11
Enrollment: 11
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to determine whether a low dose an opiate pain medication is effective for the treatment of discomfort in patients with advanced dementia. The study medication was also known as Lortab and contained both a narcotic pain medication and acetaminophen (the same pain medication as contained in Tylenol). This study was an eight-week long clinical trial for discomfort among veterans with advanced dementia who were admitted to a Nursing Home Care Unit (NHCU) at the Tuscaloosa VA Medical Center.

Detailed description: OBJECTIVES: The primary objective of the Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT) project was to determine whether low-dose opiates are effective and well tolerated for the treatment of pain (as manifest by discomfort) in patients with advanced dementia.

RESEARCH DESIGN: This study was a two-week double-blind, double-dummy, placebo-controlled, crossover trial of low-dose hydrocodone/acetaminophen (Lortab) for discomfort among veterans with a dementia, followed by six weeks of open-label therapy for patients who tolerated treatment during the first two weeks (eight weeks total treatment on study).

METHODOLOGY: After consent, patients over age 55 with dementia residing in a nursing home care unit (or at home who receive care) at Tuscaloosa VAMC who demonstrate significant discomfort (as measured by the Pain Assessment in Advanced Dementia - PAINAD) were randomized to one of two groups, using a double-blind, double-dummy, placebo-controlled, crossover design. Patients were randomly assigned to treatment with either hydrocodone/acetaminophen 2.5mg/250mg q8hrs scheduled with placebo q8hrs PRN or placebo q8hrs scheduled with hydrocodone/acetaminophen 2.5mg/250mg q8hrs PRN. After one week's treatment, patients were crossed over to the other (opposite) regimen, for a total of two weeks of blinded treatment. Patients who tolerated treatment with hydrocodone/acetaminophen were eligible for a six-week, open-label continuation phase. The primary outcome measure was pain/discomfort. Preliminary sample size calculations indicated that 42 patients (48 patients accounting for dropouts) would be needed to be enrolled over three years to detect a difference between treatments with power of .80 and two-tailed alpha of .05.

SIGNIFICANCE: There is evidence that pain is both under recognized and undertreated in long term care settings. This study hoped to make a significant contribution to the evidence base for a common and problematic situation among veterans with advanced dementia. Advances in pain and symptom control are central to the improvement of palliative care intervention for dementia patients. Low-dose opiates are the logical next category of analgesics to consider, but have been rarely studied for this purpose in this population.

Eligibility criteria: Inclusion Criteria:

* 55 years of age or older;
* Must have a diagnosis of dementia;
* Advanced stage of dementia demonstrated by a score of 6 or greater on the Functional Assessment Staging (FAST) scale;
* Unable to report pain in a reliable and consistent manner;
* Have a PAINAD score of at least 2 on two consecutive assessments (separated by at least two days) OR an average PAINAD score of at least 2 on three consecutive assessments each separated by at least two days;
* The patient must have at least one medical condition associated with pain recorded on the CPRS problem list.

Exclusion Criteria:

* The existence of an effective analgesia treatment regimen;
* Pain treatment related to angina or pain judged to be related to angina;
* Current pain treatment with opiates that cannot, in the opinion of the attending physician, be discontinued without placing the patient at risk for increased pain or opiate withdrawal;
* Current pain treatment with tramadol that cannot, in the opinion of the attending physician, be discontinued;
* Presence of necessary drug therapy that is incompatible with or has potential for clinically significant drug interaction with either hydrocodone or acetaminophen;
* A history of allergy, hypersensitivity, or intolerance to either hydrocodone or acetaminophen;
* Constipation refractory to current treatment measures or a condition that would make constipation dangerous for the patient in the opinion of the attending physician;
* The presence of liver disease, hepatic encephalopathy, or clinically significant elevation of liver function tests (LFTs), as determined by the attending physician;
* The presence of renal failure, clinically significant renal insufficiency, or clinically significant elevations of serum BUN or creatinine levels, as determined by the attending physician; OR
* Evidence, based on assessment by a geriatrician, that the apparent behavioral manifestations of discomfort are better explained by another problem (e.g., fever, infection, dehydration, delirium, psychosis)

Primary outcomes:
measure: Pain Assessment in Advanced Dementia (PAINAD)
timeFrame: Two (2) weeks
Secondary outcomes:
measure: Pain Assessment in Advanced Dementia (PAINAD)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: Tuscaloosa VA Medical Center
state: Alabama
city: Tuscaloosa
country: United States
facility: Tuscaloosa Veterans Affairs Medical Center
state: Alabama
city: Tuscaloosa
country: United States
facility: VA Medical Center, Tuscaloosa
state: Alabama
Study officials:
affiliation: VA Medical Center, Tuscaloosa
name: Andrea Snow, PhD MS BS
role: PRINCIPAL_INVESTIGATOR
References: