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

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

The purpose of this study is 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 is also known as Lortab and contains both a narcotic pain medication and the same pain medication as contained in Tylenol. The study will also assess how well patients tolerate this medication and will measure the impact that relief of discomfort has on agitation and other symptoms. This study is an eight-week long clinical trial for discomfort among veterans with advanced dementia who are admitted to a Nursing Home Care Unit (NHCU) at the Tuscaloosa VA Medical Center.

OBJECTIVES: The primary objective of the Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT) project will be 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. The secondary objectives will be to assess the tolerability of such treatment and to assess the impact of effective analgesia on agitation and other symptom burden in this population.

RESEARCH DESIGN: This study is 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 tolerate 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) will be randomized to one of two groups, using a double-blind, double-dummy, placebo-controlled, crossover design. Patients will be 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 will be crossed over to the other (opposite) regimen, for a total of two weeks of blinded treatment. Patients who tolerate treatment with hydrocodone/acetaminophen will be eligible for a six-week, open-label continuation phase. Outcome measures will include pain/discomfort, agitation, symptom burden, tolerability/adverse effects, and dropout rates. Preliminary sample size calculations indicate that 42 patients (48 patients accounting for dropouts) would need 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 underrecognized and undertreated in long term care settings. This study will 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 not been studied for this purpose in this population.

Intervention(s) in this Clinical Trial

• Drug: hydrocodone/APAP
  • Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID) during the blinded portion of the study, with potential to increase dosage to 5/500mg TID during the open-label phase if needed.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • During the one-week experimental phase, the participants will receive hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID), with liquid placebo available PRN.
• Placebo Comparator: 2
  • During the one-week experimental phase, the participants will receive a liquid placebo three times a day (TID) with hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid available PRN
• Other: 3
  • During the 6-week open-label phase, those who tolerate hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID) during the double-blind phase of the trial will enter a six-week, open-label extension phase of the study, receiving either hydrocodone/ acetaminophen at the same dose or the most appropriate formulary alternative (for those who are judged to be responders during the double-blind phase) or a higher dose (hydrocodone/acetaminophen 5/500mg TID or the most appropriate formulary alternative). Participant can also receive up to 2 PRN at the same dose as listed above, but not to exceed 2.5g of acetaminophen.

Primary Measures

• Discomfort Battery(DB), Discomfort Scale for patient with Dementia Alzheimer's Type(DS-DAT)
  • Time Frame: Eight (8) weeks
    Safety Issue?: No

Secondary Measures

• Pain Assessment in Advanced Dementia (PAINAD)
  • Time Frame: Eight (8) weeks
    Safety Issue?: No
• Computer Assisted Behavior Observation System (CABOS)
  • Time Frame: Eight (8) Weeks
    Safety Issue?: No

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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 55 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Department of Veterans Affairs U.S. Fed

Overall Clinical Trial Officials and Contacts

A. Lynn Snow, PhD MS BS Principal Investigator VA Medical Center, Tuscaloosa  

Overall Contact: Jennifer A Biladeau (205) 554-2000 Jennifer.Biladeau@va.gov

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00385684

Study ID Number: F4483I

ClinicalTrials.gov Identifier: NCT00385684

Health Authority: United States: Federal Government