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

Primary Purpose

Alzheimer Disease, Dementia, Dementia, Vascular

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
hydrocodone/APAP w placebo PRN
hydrocodone/APAP
placebo with hydrocodone/APAP PRN
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Agitation, Alzheimer Disease, Analgesics, Dementia, Narcotics, Opioid, Pain, Palliative Care, Psychomotor, Suffering, Physical

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Tuscaloosa VA Medical Center
  • Tuscaloosa Veterans Affairs Medical Center
  • VA Medical Center, Tuscaloosa

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Active Comparator

Arm Label

A1: hydrocodone/APAP w placebo PRN

A2: placebo w hydrocodone/APAP PRN

B: Open label hydrocodone/acetaminophen

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

Pain Assessment in Advanced Dementia (PAINAD)
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)
Pain intensity observational assessment for persons with severe dementia. Higher scores indicate more pain/discomfort.

Full Information

First Posted
October 6, 2006
Last Updated
November 18, 2015
Sponsor
VA Office of Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT00385684
Brief Title
Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
Acronym
LDOT
Official Title
Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Dementia, Dementia, Vascular, Pain
Keywords
Agitation, Alzheimer Disease, Analgesics, Dementia, Narcotics, Opioid, Pain, Palliative Care, Psychomotor, Suffering, Physical

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A1: hydrocodone/APAP w placebo PRN
Arm Type
Experimental
Arm 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.
Arm Title
A2: placebo w hydrocodone/APAP PRN
Arm Type
Placebo Comparator
Arm 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.
Arm Title
B: Open label hydrocodone/acetaminophen
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
hydrocodone/APAP w placebo PRN
Other Intervention Name(s)
Lortab
Intervention Description
Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID). With liquid placebo available PRN.
Intervention Type
Drug
Intervention Name(s)
hydrocodone/APAP
Other Intervention Name(s)
Lortab
Intervention Description
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
Intervention Name(s)
placebo with hydrocodone/APAP PRN
Other Intervention Name(s)
placebo with Lortab PRN
Intervention Description
Liquid placebo PRN. Also available PRN is Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid.
Primary Outcome Measure Information:
Title
Pain Assessment in Advanced Dementia (PAINAD)
Description
Pain intensity observational assessment for persons with severe dementia. Higher scores indicate more pain/discomfort. Scale range is 0-10.
Time Frame
Two (2) weeks
Secondary Outcome Measure Information:
Title
Pain Assessment in Advanced Dementia (PAINAD)
Description
Pain intensity observational assessment for persons with severe dementia. Higher scores indicate more pain/discomfort.
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Snow, PhD MS BS
Organizational Affiliation
VA Medical Center, Tuscaloosa
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tuscaloosa VA Medical Center
City
Tuscaloosa
State/Province
Alabama
ZIP/Postal Code
35404
Country
United States
Facility Name
Tuscaloosa Veterans Affairs Medical Center
City
Tuscaloosa
State/Province
Alabama
ZIP/Postal Code
35404
Country
United States
Facility Name
VA Medical Center, Tuscaloosa
City
Tuscaloosa
State/Province
Alabama
ZIP/Postal Code
35404
Country
United States

12. IPD Sharing Statement

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

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