Clinical trial NCT00422981: Safety, Tolerability and Efficacy Study to Evaluate Subjects With Mild Cognitive Impairment
Official title: A Phase 2, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Effect on Cognitive Function of AL-108 After 12 Weeks of Intranasal Administration in Subjects With Mild Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild Cognitive Impairment, So Stated
Keywords: Dementia
Memory
Alzheimers
Cognition
Mind
Aging
Lead sponsor: Allon Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-01-17
Enrollment: 144
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to find out if different doses of Investigational Drug are safe, tolerable, and if they have an effect on Mild Cognitive Impairment (MCI).

Detailed description: Pre-Clinical experiments indicate the AL-108 compound has neuroprotective, cognitive protective and neurotrophic properties; therefore, the compound could be tested in a variety of human diseases. Human diseases include Cognitive impairment associated with aging or neurodegenerative diseases such as Alzheimer's Disease.

This clinical trial aims at providing the dose rationale as well as safety and tolerability information for AL-108 as evaluated after 12 weeks of intranasal administration in subjects with Mild Cognitive Impairment (MCI).

There are currently no drugs approved for the treatment of MCI nor accepted treatment or standard treatment approach.

Eligibility criteria: Inclusion Criteria:

* Is male or female, at 55-85 years of age (inclusive) at screening
* Self-reported memory complaint, corroborated by spouse or companion as appropriate.
* Wechsler Memory Scale III (WMS-III) age-adjusted Logical Memory II score ≤ 5.
* Mini-Mental State Exam (MMSE) ≥24.
* Center for Epidemiologic Studies-Depression (CES-D) score \<27.
* Normal thyroid function, defined as TSH, T3 and T4 within normal limits.
* Agree not to consume alcoholic beverages within 8 hours of each study visit.
* Willing and able to sign informed consent and complete the CTB and all other tests and procedures as listed in the protocol.
* Fluently reads and speaks English.
* Female subjects must be surgically sterile or post-menopausal for at least 2 years. If \<2 years post-menopausal, then a follicle stimulating hormone (FSH) ≥40 mIU/mL must be obtained.

Exclusion Criteria:

* Subjects who have any significant, untreated psychiatric illness or any CNS condition (such as schizophrenia, Parkinson's disease, stroke, etc.) that could interfere with the study evaluations or procedures or which poses an additional risk. Subjects with a history of uncomplicated depression may participate if in remission and on a stable dose of antidepressant medication for at least 2 months.
* History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
* History of alcohol or substance abuse or dependence within the past year.
* Acute infective sinusitis.
* History or presence of an abnormality of the external or internal structures of the nose or nasopharynx, except for surgical correction of the nasal septum or a "broken nose" at least 2 years previously, or surgical repair of cleft palate when \<30 years of age.
* Use of medications that are known to cause frank obtundation of cognition
* Use of any approved or investigational medication for Alzheimer's Disease within 3 months of screening
* History of or current significant systemic disease judged to interfere with the study evaluations or likely to be a safety concern.
* Untreated sleep apnea or treatment for sleep apnea for \<3 months.
* Abnormal clinical laboratory test results, specifically: Alanine transaminase (ALT) or aspartate transaminase (AST) \>2 х the upper limit of normal (ULN),Hematology \<80% the lower limit of normal, Creatinine ≥2 mg/dL and ,Other clinical laboratory values or vital signs considered clinically significant in the opinion of the Investigator.
* Treatment with any investigational drug, biologic, or device within the previous 30 days prior to screening.
* Surgery involving general anesthesia within the past 3 months or planned surgery requiring general anesthesia during the study period.

Primary outcomes:
measure: Change from baseline to Week 12 on the Composite Memory Variable
timeFrame: 12 weeks
Secondary outcomes:
measure: Changes in the Composite Memory Variable from baseline to weeks 4, 8, and 16
timeFrame: 16 weeks
measure: Changes in test battery individual items from baseline to endpoints (weeks 4, 8, 12, and 16).
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Pivotal Research
state: Arizona
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network
state: California
city: National City
country: United States
facility: Synergy Research
state: California
city: San Diego
country: United States
facility: Pacific Research Network, Inc
state: California
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Vero Beach
country: United States
facility: Clinical Research Center of Indian River Medical Center
state: Florida
city: Hoffman Estates
country: United States
facility: Comprehensive Neuroscience
state: Illinois
city: Long Branch
country: United States
facility: The Memory Enhancement Center of America
state: New Jersey
city: Brooklyn
country: United States
facility: SPRI Clinical trials
state: New York
city: Wilmington
country: United States
facility: Memory Assessment and Research Services
state: North Carolina
city: Toledo
country: United States
facility: Neurology & Neuroscience Center of Ohio
state: Ohio
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Tennessee
city: Austin
country: United States
facility: Senior Adults Speciality Research
state: Texas
Study officials:
affiliation: Memory Assessment and Research Services
name: Donald E Schmechel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morimoto BH, Schmechel D, Hirman J, Blackwell A, Keith J, Gold M; AL-108-211 Study. A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. Dement Geriatr Cogn Disord. 2013;35(5-6):325-36. doi: 10.1159/000348347. Epub 2013 Apr 13.