Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)

Conditions
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Alzheimer Disease, Dementia, Dementia, Vascular, Pain

Intervention / Treatment
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* Drug: hydrocodone/APAP w placebo PRN
* Drug: hydrocodone/APAP
* Drug: placebo with hydrocodone/APAP PRN


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 55 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1: hydrocodone/APAP w placebo PRN<br>This is a fully crossed study, each participant serves as his own control. Phase A (closed label) has two arms: A1 is the experimental and A2 is the placebo comparator. Participants are randomized to either A1 for 1 week then A2 for 1 week OR A2 for 1 week then A1 for one week. A1: hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid TID, with liquid placebo available PRN. A2: liquid placebo TID with hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid PRN. | Drug: hydrocodone/APAP w placebo PRN<br>* Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID). With liquid placebo available PRN.<br>* Other names: Lortab;|
| Placebo Comparator: A2: placebo w hydrocodone/APAP PRN<br>This is a fully crossed study, each participant serves as his own control. Phase A: Participants are randomized to either A1 for 1 week then A2 for 1 week OR A2 for 1 week then A1 for one week. A1: hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid TID, with liquid placebo available PRN. A2: liquid placebo TID with hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid PRN. | Drug: placebo with hydrocodone/APAP PRN<br>* Liquid placebo PRN. Also available PRN is Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid.<br>* Other names: placebo with Lortab PRN;|
| Active Comparator: B: Open label hydrocodone/acetaminophen<br>Phase B: If tolerated study medication during Phase A (i.e., the closed label, double-blind phase of the trial) then enter a six-week, open-label phase. Participants judged as responders during Phase A continue the same dose of study medication. Otherwise, moved to a higher dose (hydrocodone/acetaminophen 5/500mg TID or the most appropriate formulary alternative). Participant can also receive up to 2 PRN administrations at the same dose levels as listed above, but not to exceed 2.5g of acetaminophen. | Drug: hydrocodone/APAP<br>* Participants judged as responders during Phase A continue the same dose of study medication (hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid TID). Otherwise, moved to a higher dose (hydrocodone/acetaminophen 5/500mg TID or the most appropriate formulary alternative). Participant can also receive up to 2 PRN administrations at the same dose levels as listed above, but not to exceed 2.5g of acetaminophen.<br>* Other names: Lortab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Assessment in Advanced Dementia (PAINAD) | Pain intensity observational assessment for persons with severe dementia. Higher scores indicate more pain/discomfort. Scale range is 0-10. | Two (2) weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Assessment in Advanced Dementia (PAINAD) | Pain intensity observational assessment for persons with severe dementia. Higher scores indicate more pain/discomfort. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Agitation, Alzheimer Disease, Analgesics, Dementia, Narcotics, Opioid, Pain, Palliative Care, Psychomotor, Suffering, Physical