Phase 2
N=77
Treatment of Psychosis and Agitation in Alzheimer's Disease
Alzheimer's Disease · Psychosis · Agitation
Bottom Line
View on ClinicalTrials.gov: NCT02129348 ↗Enrolled (actual)
77
Serious AEs
28.6%
Results posted
Aug 2021
Primary outcome: Primary: Change in Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score — 3.2; 2.5 score on a scale — p=0.53
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Lithium (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- New York State Psychiatric Institute
- Primary completion
- Jan 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score |
3.2; 2.5 | 0.53 |
| SECONDARY Clinical Responder Defined as a 30% Decrease in NPI Core Score (Sum Score of NPI Domains of Agitation/Aggression, Delusions and Hallucinations) Together With a Clinical Global Impression (CGI) Behavior Change Score of 1 or 2 |
12; 7 | 0.26 |
| SECONDARY Clinical Global Impression (CGI) Behavior Change |
12; 8 | 0.25 |
| SECONDARY Young Mania Rating Scale |
3.1; 1.1 | 0.21 |
| SECONDARY Treatment Emergent Signs and Symptoms |
0.6; 0.7 | 0.91 |
| SECONDARY Simpson-Angus Scale |
-0.0; 0.0 | 0.94 |
| SECONDARY Basic Activities of Daily Living (BADL) |
0.3; 0.1 | 0.63 |
| SECONDARY Zarit Caregiver Burden Interview |
2.8; -0.4 | 0.24 |
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.
Eligibility Criteria
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.
Contraindications to lithium in this study include: resting tremor causing functional impairment, history of falls in the last month, untreated thyroid disease or any abnormal thyroid function test (T3, T4, or TSH), creatinine level greater than 1.5 mg/100ml or a glomerular filtration rate less than 44ml/min/ 1.73m2; blood pressure > 150/90 mm Hg; heart rate 460 ms at the time of baseline EKG is an exclusion criterion for treatment.
- Hypernatremia as determined by serum sodium level > 150 meq/L.
Data sourced from ClinicalTrials.gov (NCT02129348). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.