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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development
ClinicalTrials.gov Identifier:
NCT00385684
First received: October 6, 2006
Last updated: November 18, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Alzheimer Disease
Dementia
Dementia, Vascular
Pain
Drug: hydrocodone/APAP w placebo PRN
Drug: hydrocodone/APAP
Drug: placebo with hydrocodone/APAP PRN
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)

Resource links provided by NLM:


Further study details as provided by VA Office of Research and Development:

Primary Outcome Measures:
  • Pain Assessment in Advanced Dementia (PAINAD) [ Time Frame: Two (2) weeks ] [ Designated as safety issue: No ]
    Pain intensity observational assessment for persons with severe dementia. Higher scores indicate more pain/discomfort. Scale range is 0-10.


Secondary Outcome Measures:
  • Pain Assessment in Advanced Dementia (PAINAD) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Pain intensity observational assessment for persons with severe dementia. Higher scores indicate more pain/discomfort.


Enrollment: 11
Study Start Date: October 2007
Study Completion Date: June 2014
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: hydrocodone/APAP w placebo PRN
Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID). With liquid placebo available PRN.
Other Name: Lortab
Placebo Comparator: 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.
Drug: placebo with hydrocodone/APAP PRN
Liquid placebo PRN. Also available PRN is Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid.
Other Name: placebo with Lortab PRN
Active Comparator: 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.
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.
Other Name: Lortab

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

Ages Eligible for Study:   55 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00385684

Locations
United States, Alabama
Tuscaloosa VA Medical Center
Tuscaloosa, Alabama, United States, 35404
Tuscaloosa Veterans Affairs Medical Center
Tuscaloosa, Alabama, United States, 35404
VA Medical Center, Tuscaloosa
Tuscaloosa, Alabama, United States, 35404
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Principal Investigator: Andrea Snow, PhD MS BS VA Medical Center, Tuscaloosa
  More Information

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT00385684     History of Changes
Other Study ID Numbers: F4483-I 
Study First Received: October 6, 2006
Results First Received: June 2, 2014
Last Updated: November 18, 2015
Health Authority: United States: Federal Government

Keywords provided by VA Office of Research and Development:
Agitation
Alzheimer Disease
Analgesics
Dementia
Narcotics
Opioid
Pain
Palliative Care
Psychomotor
Suffering, Physical

Additional relevant MeSH terms:
Dementia
Dementia, Vascular
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cerebrovascular Disorders
Intracranial Arteriosclerosis
Intracranial Arterial Diseases
Leukoencephalopathies
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Acetaminophen
Acetaminophen, hydrocodone drug combination
Hydrocodone
Oxycodone
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Analgesics, Opioid
Narcotics

ClinicalTrials.gov processed this record on August 23, 2016