Treatment of Psychosis and Agitation in Alzheimer's Disease (NCT02129348) | Clinical Trial Compass
CompletedPhase 2
Treatment of Psychosis and Agitation in Alzheimer's Disease
United States77 participantsStarted 2014-06
Plain-language summary
Clinically, many patients with AD show no response or minimal response to antipsychotics for symptoms of agitation/aggression or psychosis, or they have intolerable side effects on these medications. Antipsychotics have a wide range of side effects, including the risk of increased mortality (60-70% higher rate of death on antipsychotic compared to placebo) that led to an FDA black box warning for patients with dementia; a more recent review and meta-analysis showed a 54% increased risk of mortality. In addition, some patients show only partial response to antipsychotics and symptoms persist. For these reasons, the investigators need to study alternative treatment strategies. Currently, there is no FDA-approved medication for the treatment of psychosis or agitation in AD.
The investigators innovative project will examine the efficacy and side effects of low dose lithium treatment of agitation/aggression with or without psychosis in 80 patients with AD in a randomized, doubleblind, placebo-controlled, 12-week trial (essentially a Phase II trial). The results will determine the potential for a large-scale clinical trial (Phase III) to establish the utility of lithium in these patients.
Who can participate
SexALL
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Inclusion criteria
✓. Male and female adults.
✓. Diagnosis of possible or probable AD by standard NIA criteria (McKahnn et al, 1984; McKhann et all, 2011)
✓. Folstein MMSE 5-26 out of 30
✓. Neuropsychiatric Inventory (NPI) agitation/aggression subscale score \> 4. On each subscale (frequency X severity), a score higher than 4 represents moderate to severe symptoms.
✓. Female patients need to be post-menopausal
✓. Availability of informant; patients without an informant will not be recruited. Patients who lack capacity must have a surrogate.
Exclusion criteria
✕. Medical contraindication to lithium treatment or prior history of intolerability to lithium treatment.
✕. Medications, in combination with lithium, known to have adverse renal effects, including therapeutic or higher doses of diuretics, i.e. hydrochlorothiazide greater than 25mg daily or furosemide greater than 10mg daily. Whenever feasible, patients receiving concomitant antidepressants or antipsychotics will be washed off these medications for at least 24 hours before starting lithium. Patients who do not wish to discontinue antipsychotics or antidepressants, typically because of family member/caregiver objection, will be allowed to enter the trial provided there is no contraindication to concomitant lithium use with that specific psychotropic medication. During the trial, patients will be permitted to receive lorazepam as needed up to 1 mg/day for anxiety/insomnia, and non-benzodiazepine hypnotics, e.g., zolpidem.
What they're measuring
1
Change in Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score
✕. Current clinical diagnosis of schizophrenia, schizoaffective disorder, other psychosis, or bipolar 1 disorder (DSM-IV TR criteria).
✕. Current or recent (past 6 months) alcohol or substance dependence (DSM-IV TR criteria).
✕. Current major depression or suicidality as assessed by the study psychiatrist.
✕. Suicidal behavior or dangerous behavior with serious safety risk or risk of physical harm to self or others.
✕. Parkinson's disease, Lewy body disease, multiple sclerosis, CNS infection, Huntington's disease, amyotrophic lateral sclerosis, other major neurological disorder.
✕. Clinical stroke with residual neurological deficits. MRI findings of cerebrovascular disease (small infarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion.