Safety and Tolerability of Antioxidant (AT-001)for Reducing Brain Oxidative Stress

NCT01731093 | Completed Phase 1 DMC

• 1 other identifier: 11-0967-F2L
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety, bioavailability, and effectiveness of an organic yeast-selenium compound in reducing brain oxidative stress. Oxidative stress in the brain has been linked to a variety oif disorders including Alzheimer's disease. Selenium is a very powerful antioxidant that could prove useful in reducing the harmful effects of oxidative stress in the brain and may help prevent diseases such as Alzheimer's. Our recent work has demonstrated that the specific type of selenium compound greatly influences it's ability to enhance brain health and prevent Alzheimer changes in mouse models of this disease. This study will enroll 24 participants and will allow us to test the hypotheses that yeast-selenium supplementation is safe in the elderly, and that our specific formulation reduces brain oxidative stress.

Conditions

Oxidative Stress

Keywords

aged; health; brain

Outcome Measures

Primary Outcomes (1)

• Frequency of adverse events

  Safety and tolerability will be assessed by analysis of adverse events, including symptoms and abnormal findings on physical examinations and standard laboratory tests (serum chemistry, hematology, and urinalysis).

  Baseline to week 14

Secondary Outcomes (3)

• Change in serum selenium levels

  Baseline to week 12

• Change in cerebrospinal fluid selenium levels

  Baseline to week 12

• Change in serum, urine, and cerebrospinal fluid isoprostanes

  Baseline to week 12

Study Arms (2)

AT-001

EXPERIMENTAL

AT-001

Drug: AT-001

Placebo

PLACEBO COMPARATOR

Matching placebo.

Drug: Placebo

Interventions

AT-001 DRUG

AT-001

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Men and women age \> 64 years.
• Not demented by Hachinski Ischemic Index (≤ 4)
• English-speaking, to ensure compliance with study visit procedures.
• Female participants must not be pregnant or of childbearing potential, i.e. either surgically sterile or postmenopausal for \> 1 year.
• Stable medical condition for three months prior to screening visit, with no clinically significant abnormalities of hepatic, renal, and hematologic function defined as follows: WBC within normal limits, platelets \> 100,000, hemoglobin ≥11 mg/dL, srum creatinine ≤ 1.8 mg/dL, AST or ALT ≤ 1.5 ULN, no clinically significant abnormalities of other laboratory studies (CBC, chemistry panel, urinalysis).
• Non-diabetic confirmed by fasting serum glucose \<126 mg/dL and on no oral hypoglycemic agents or insulin treatment.
• Stable medications for 12 weeks prior to screening visit.
• Able to ingest oral medications.
• No contraindication to baseline MRI (metallic implants, pacemakers, shrapnel…etc.).
• Physically acceptable for this study as confirmed by medical history, physical exam, neurological exam and clinical tests.

You may not qualify if:

• Significant neurologic disease such as Parkinson's disease, stroke, brain tumor, multiple sclerosis or seizure disorder.
• Major depression in past 12 months (DSM-IV criteria) major mental illness such as schizophrenia, or recent (in past 12 months) alcohol or substance abuse.
• History of invasive cancer within the past two years (excluding non-melanoma skin cancer).
• Contra-indications to lumbar puncture (bleeding disorder, platelet count \< 100,000, anticoagulant treatment, major structural abnormality or sepsis in the area of the lumbosacral spine, previous lower back surgery that would make LP technically difficult, hypersensitivity to lidocaine).
• Other conditions that will contribute to oxidative stress including but not limited to current smokers of cigarettes or cigars (within past month), history of alcohol or drug abuse as determined by medical history review.
• Known sensitivity, intolerance, or allergies to yeast or selenium-based compounds.
• Daily intake of more than 75 µg selenium/day (US RDA) in the 90 days prior to enrollment.
• Use of any investigational agents within 90 days prior to screening.
• Major surgery within eight weeks prior to the Baseline Visit.
• Severe unstable medical illnesses, including uncontrolled cardiac conditions or heart failure (New York Heart Association Class III or IV).
• Extremes of body weight (\<100 or \>240 lbs) to exclude upper and lower 5th percentiles for age that may influence PK and safety data.
• Residence in a skilled nursing facility.
• Blindness, deafness, language difficulties or any other disability that may prevent the subject from participating or cooperating in the protocol.
• Safety laboratory values deemed clinically significant by investigator.
• Excluded Medications:

Sponsors & Collaborators

• Alltech Life Sciences Inc.: lead

Study Sites (1)

University of Kentucky Alzheimer's Disease Research Center

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Interventions

caficrestat

Study Officials

• Gregory A Jicha, MD, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

• Ronan Power, PhD

  Alltech Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2012
• First Posted: November 21, 2012
• Study Start: March 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 23, 2014

Record last verified: 2014-01

Locations

US (1)