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

NCT ID: NCT00385684

Last Updated: 2015-11-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-31

Study Completion Date

2014-06-30

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.

Conditions

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Alzheimer Disease Dementia Dementia, Vascular Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A1: hydrocodone/APAP w placebo PRN

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.

Group Type EXPERIMENTAL

hydrocodone/APAP w placebo PRN

Intervention Type DRUG

Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID). With liquid placebo available PRN.

A2: placebo w hydrocodone/APAP PRN

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.

Group Type PLACEBO_COMPARATOR

placebo with hydrocodone/APAP PRN

Intervention Type DRUG

Liquid placebo PRN. Also available PRN is Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid.

B: Open label hydrocodone/acetaminophen

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.

Group Type ACTIVE_COMPARATOR

hydrocodone/APAP

Intervention Type DRUG

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.

Interventions

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hydrocodone/APAP w placebo PRN

Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID). With liquid placebo available PRN.

Intervention Type DRUG

hydrocodone/APAP

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.

Intervention Type DRUG

placebo with hydrocodone/APAP PRN

Liquid placebo PRN. Also available PRN is Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid.

Intervention Type DRUG

Other Intervention Names

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Lortab Lortab placebo with Lortab PRN

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)
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrea Snow, PhD MS BS

Role: PRINCIPAL_INVESTIGATOR

VA Medical Center, Tuscaloosa

Locations

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Tuscaloosa VA Medical Center

Tuscaloosa, Alabama, United States

Site Status

Tuscaloosa Veterans Affairs Medical Center

Tuscaloosa, Alabama, United States

Site Status

VA Medical Center, Tuscaloosa

Tuscaloosa, Alabama, United States

Site Status

Countries

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United States

Other Identifiers

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F4483-I

Identifier Type: -

Identifier Source: org_study_id