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

VA Office of Research and Development

Status and phase: Completed; Phase 4

Conditions: Alzheimer Disease; Dementia, Vascular; Pain; Dementia

Treatments: Drug: placebo with hydrocodone/APAP PRN; Drug: hydrocodone/APAP; Drug: hydrocodone/APAP w placebo PRN

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT00385684

F4483-I

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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11 participants in 3 patient groups, including a placebo group

A1: hydrocodone/APAP w placebo PRN

Experimental group

Description:

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.

Treatment:

Drug: hydrocodone/APAP w placebo PRN

A2: placebo w hydrocodone/APAP PRN

Placebo Comparator group

Description:

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.

Treatment:

Drug: placebo with hydrocodone/APAP PRN

B: Open label hydrocodone/acetaminophen

Active Comparator group

Description:

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.

Treatment:

Drug: hydrocodone/APAP