Alzheimer DiseasePhase 4LDOTNCT00385684
Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
A Phase 4 study testing hydrocodone/APAP in people with Alzheimer Disease and Dementia, run by VA Office of Research and Development at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Alzheimer Disease, Dementia, Dementia, Vascular
- What is being tested?
- hydrocodone/APAP
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2007to Jun 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Tuscaloosa VA Medical Center
Tuscaloosa, Alabama, 35404
Tuscaloosa Veterans Affairs Medical Center
Tuscaloosa, Alabama, 35404
VA Medical Center, Tuscaloosa
Tuscaloosa, Alabama, 35404
About this study
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.
Read the 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.
- Conditions
- Alzheimer Disease, Dementia, Dementia, Vascular, Pain
- Being tested
- hydrocodone/APAP w placebo PRN, hydrocodone/APAP, placebo with hydrocodone/APAP PRN
- Keywords
- Agitation, Alzheimer Disease, Analgesics, Dementia, Narcotics, Opioid, Pain, Palliative Care, Psychomotor, Suffering, Physical
- Medical subject headings
- Alzheimer Disease, Dementia, Dementia, Vascular, Pain, Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hydrocodone/APAP w placebo PRNDrug
Also called Lortab
Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID). With liquid placebo available PRN.
hydrocodone/APAPDrug
Also called Lortab
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.
placebo with hydrocodone/APAP PRNDrug
Also called placebo with Lortab PRN
Liquid placebo PRN. Also available PRN is Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid.
| Study group | Role | What they receive |
|---|---|---|
| A1: hydrocodone/APAP w placebo PRN | Experimental | 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. Receives: Drug: hydrocodone/APAP w placebo PRN |
| A2: placebo w hydrocodone/APAP PRN | Placebo comparator | 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. Receives: Drug: placebo with hydrocodone/APAP PRN |
| B: Open label hydrocodone/acetaminophen | Active comparator | 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. Receives: Drug: hydrocodone/APAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Two (2) weeks
Secondary outcomes (1)
Pain Assessment in Advanced Dementia (PAINAD)
Pain intensity observational assessment for persons with severe dementia. Higher scores indicate more pain/discomfort.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2006 (estimated)
- Study startOct 2007
- Primary completionDec 2011
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Andrea Snow, PhD MS BS, Principal investigator, VA Medical Center, Tuscaloosa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00385684
- Sponsor's protocol ID
- F4483-I
- Acronym
- LDOT
- Status last verified
- Nov 2015
- First submitted
- 6 Oct 2006
- Last updated
- 20 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
- ClinicalTrials.gov ID
- NCT00385684
- Acronym / sponsor ID
- LDOT / F4483-I
- Conditions
- Alzheimer Disease, Dementia, Dementia, Vascular, Pain
- Keywords
- Agitation, Alzheimer Disease, Analgesics, Dementia, Narcotics, Opioid, Pain, Palliative Care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- Oct 2007
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 11 Oct 2006 (estimated)
- Results
- Posted 20 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A1: hydrocodone/APAP w placebo PRN | Experimental | Drug: hydrocodone/APAP w placebo PRNThis 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. |
| A2: placebo w hydrocodone/APAP PRN | Placebo comparator | Drug: placebo with hydrocodone/APAP PRNThis 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. |
| B: Open label hydrocodone/acetaminophen | Active comparator | Drug: hydrocodone/APAPPhase 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. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hydrocodone/APAP w placebo PRNAlso: LortabHydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid three times daily (TID). With liquid placebo available PRN. | Drug | A1: hydrocodone/APAP w placebo PRN |
| hydrocodone/APAPAlso: LortabParticipants 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. | Drug | B: Open label hydrocodone/acetaminophen |
| placebo with hydrocodone/APAP PRNAlso: placebo with Lortab PRNLiquid placebo PRN. Also available PRN is Hydrocodone/acetaminophen 2.5/167 mg per 5 ml liquid. | Drug | A2: placebo w hydrocodone/APAP PRN |
Primary outcome
Pain Assessment in Advanced Dementia (PAINAD)
Time frame: Two (2) weeks
Pain intensity observational assessment for persons with severe dementia. Higher scores indicate more pain/discomfort. Scale range is 0-10.
1 secondary outcome
Pain Assessment in Advanced Dementia (PAINAD)
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Snow, PhD MS BS principal investigator
VA Medical Center, Tuscaloosa
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing hydrocodone/APAP in people with Alzheimer Disease and Dementia, run by VA Office of Research and Development at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Assessment in Advanced Dementia (PAINAD) (time frame: Two (2) weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2015.