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

Sponsor:	Department of Veterans Affairs
Information provided by (Responsible Party):	Department of Veterans Affairs
ClinicalTrials.gov Identifier:	NCT00385684

Purpose

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.

Condition	Intervention	Phase
Alzheimer Disease Dementia Dementia, Vascular Pain	Drug: hydrocodone/APAP	Phase IV

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:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease Dementia

Drug Information available for: Acetaminophen CT 2584 Hydrocodone Hydrocodone bitartrate Hycodan

U.S. FDA Resources

Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:

Discomfort Battery(DB), Discomfort Scale for patient with Dementia Alzheimer's Type(DS-DAT) [ Time Frame: Eight (8) weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pain Assessment in Advanced Dementia (PAINAD) [ Time Frame: Eight (8) weeks ] [ Designated as safety issue: No ]
Computer Assisted Behavior Observation System (CABOS) [ Time Frame: Eight (8) Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	48
Study Start Date:	October 2007
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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. Other Name: Lortab
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	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. Other Name: Lortab
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.	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. Other Name: Lortab

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	55 Years and older
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

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

Contacts

Contact: Jennifer A Biladeau	(205) 554-2000 ext 3274	Jennifer.Biladeau@va.gov
Contact: Beverly Whitfield, MA	(205) 554-2000 ext 2733	beverly.whitfield@va.gov

Locations

United States, Alabama
VA Medical Center, Tuscaloosa	Recruiting
Tuscaloosa, Alabama, United States, 35404
Contact: Lori L Davis, MD AB (205) 554-3819 lori.davis@va.gov
Contact: Julie R Wakefield (205) 554-2000 ext 3674 Julie.Wakefield@va.gov
Principal Investigator: A. Lynn Snow, PhD MS BS
Sub-Investigator: Laura Jackson
Sub-Investigator: Jessie McAlpine, BS
Sub-Investigator: Dedria Smith
Sub-Investigator: Jennifer Ann Biladeau

Sponsors and Collaborators

Department of Veterans Affairs

Investigators

Principal Investigator:

A. Lynn Snow, PhD MS BS

VA Medical Center, Tuscaloosa

More Information

No publications provided

Responsible Party:	Department of Veterans Affairs
ClinicalTrials.gov Identifier:	NCT00385684 History of Changes
Other Study ID Numbers:	F4483I
Study First Received:	October 6, 2006
Last Updated:	September 14, 2011
Health Authority:	United States: Federal Government

Keywords provided by Department of Veterans Affairs:

Agitation
Alzheimer Disease
Analgesics
Dementia
Narcotics

Opioid
Pain
Palliative Care
Psychomotor
Suffering, Physical

Additional relevant MeSH terms:

Alzheimer Disease
Dementia
Dementia, Vascular
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive 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
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012