Trial record 6 of 69 for:    agitation and alzheimer's

Treatment of Psychosis and Agitation in Alzheimer's Disease

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by New York State Psychiatric Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT02129348
First received: April 29, 2014
Last updated: May 1, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Psychosis
Agitation
Drug: Lithium
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Treatment of Psychosis and Agitation in Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Change in Neuropsychiatric Inventory (NPI) Score [ Time Frame: Screening, Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12 ] [ Designated as safety issue: No ]
    Assessment used to examine behavioral issues and disturbances in patients with dementia. Each behavior is assessed for frequency and severity by the rater.


Secondary Outcome Measures:
  • Clinical Global Impression (CGI) Global [ Time Frame: Screening, Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12 ] [ Designated as safety issue: No ]
    Used to assess a patient's overall functioning prior to, and after taking the study medication (Lithium or placebo).

  • Clinical Global Impression (CGI) Behavior [ Time Frame: Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12 ] [ Designated as safety issue: No ]
    Assessment used to determine changes in the patients behavior prior to, and after beginning study medication (Lithium or placebo).

  • Young Mania Rating Scale [ Time Frame: Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12 ] [ Designated as safety issue: No ]
    Used to assess manic symptoms experienced by the patient in the prior two days. Each mania item on the scale is rated for severity.

  • Treatment Emergent Signs and Symptoms (TESS) [ Time Frame: Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12 ] [ Designated as safety issue: No ]
    Scale used to assess if symptoms not present at screening emerge after treatment begins. Each symptom is assigned a "yes" or "no" response based on patient and caregiver report.

  • Simpson-Angus Scale [ Time Frame: Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12 ] [ Designated as safety issue: No ]
    Five point scale used to assess pseudoparkinsonism in patients. Symptoms assess include gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation.

  • Basic Activities of Daily Living (BADL) [ Time Frame: Week 4, Week 8, Week 10, Week 12 ] [ Designated as safety issue: No ]
    Assesses if the patient can perform six basic ADLs on his own. These include bathing, dressing, toileting, transferring, continence, and feeding.

  • Zarit Caregiver Burden Interview [ Time Frame: Week 0, Week 4, Week 8, Week 10, Week 12 ] [ Designated as safety issue: No ]
    Twenty-two item questionnaire, where the caregiver is asked to rank statements on a 5-point scale (never to nearly always).

  • Clinical Dementia Rating Scale (CDR) [ Time Frame: Week 0, Week 12 ] [ Designated as safety issue: No ]
    Scale used to rate the severity of dementia symptoms raging from 0-3.


Other Outcome Measures:
  • Selective Reminding Test Immediate and Delayed Recall (SRT) [ Time Frame: Week 0, Week 12 ] [ Designated as safety issue: No ]
    Neuropsychological test used to assess a patient's ability to remember a list of 12 words. The patient is asked to name as many words as he can remember across 6 trials. After a 15 minute delay, the patient is asked to recall as many words as he can remember. The patient is visually cued for the words that he cannot recall.

  • Folstein Mini-Mental Status Exam [ Time Frame: Screening, Week 12 ] [ Designated as safety issue: No ]
    30 item questionnaire used to assess degree of cognitive impairment. Orientation, registration, attention/calculation, recall, language, repetitions and commands are assessed,


Estimated Enrollment: 80
Study Start Date: June 2014
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lithium Treatment Group

The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on real lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).

Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.

Drug: Lithium
Other Name: lithium carbonate
Placebo Comparator: Placebo Group

The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).

Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.

Drug: Placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   55 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 55-95 years
  2. Diagnosis of possible or probable AD by standard NIA criteria (McKahnn et al, 1984; McKhann et all, 2011)
  3. Folstein MMSE 5-26 out of 30
  4. Neuropsychiatric Inventory (NPI) agitation/aggression subscale score > 4. On each subscale (frequency X severity), a score higher than 4 represents moderate to severe symptoms.
  5. Female patients need to be post-menopausal
  6. Availability of informant; patients without an informant will not be recruited. Patients who lack capacity must have a surrogate.

Exclusion Criteria:

  1. 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 < 60ml/min/ 1.73m2; blood pressure > 150/90 mm Hg; heart rate < 50 bpm; unstable cardiac disease based on history, physical examination, and ECG.

  2. 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 2 mg/day for anxiety/insomnia, and non-benzodiazepine hypnotics, e.g., zolpidem.
  3. Current clinical diagnosis of schizophrenia, schizoaffective disorder, other psychosis, or bipolar 1 disorder (DSM-IV TR criteria).
  4. Current or recent (past 6 months) alcohol or substance dependence (DSM-IV TR criteria).
  5. Current major depression or suicidality as assessed by the study psychiatrist.
  6. Parkinson's disease, Lewy body disease, multiple sclerosis, CNS infection, Huntington's disease, amyotrophic lateral sclerosis, other major neurological disorder.
  7. Clinical stroke with residual neurological deficits. MRI findings of cerebrovascular disease (smallinfarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion.
  8. Acute, severe, unstable medical illness. For cancer, patients with active illness or metastases will be excluded, but past history of successfully treated cancer will not lead to exclusion.
  9. QTc interval > 460 ms at the time of baseline EKG is an exclusion criterion for treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02129348

Contacts
Contact: DP Devanand, MD 646 774 8658 ext 8658 dpd3@columbia.edu
Contact: Gregory H Pelton, MD 646 774 8669 ext 8669 ghp4@columbia.edu

Locations
United States, New York
New York State Psychiatric Institute Not yet recruiting
New York, New York, United States, 10032
Contact: Kristina D'Antonio, BS    646-774-8668 ext 8668    dantonk@nyspi.columbia.edu   
Principal Investigator: DP Devanand, MD         
Sub-Investigator: Gregory Pelton, MD         
Sub-Investigator: Edward Huey, MD         
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: DP Devanand, MD Columbia University
  More Information

Publications:

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT02129348     History of Changes
Other Study ID Numbers: 6915, 1R01AG047146-01
Study First Received: April 29, 2014
Last Updated: May 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York State Psychiatric Institute:
Alzheimer's disease
psychosis
agitation
aggression
Lithium
delusions
hallucinations

Additional relevant MeSH terms:
Alzheimer Disease
Psychomotor Agitation
Mental Disorders
Psychotic Disorders
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Schizophrenia and Disorders with Psychotic Features
Dyskinesias
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Lithium
Lithium Carbonate
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014