Trial record 2 of 6 for:    gammagard alzheimer

Study of Intravenous Immunoglobulin in Amnestic Mild Cognitive Impairment (MCI)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Shawn Kile, M.D., Sutter Health
ClinicalTrials.gov Identifier:
NCT01300728
First received: February 22, 2011
Last updated: December 12, 2012
Last verified: December 2012
  Purpose

Patients with mild cognitive impairment (MCI) are a group recognized at being at high risk of progressing to Alzheimer disease. Treatment of MCI with immunotherapy with intravenous immunoglobulins (IVIG) could potentially reduce the risk of progression to Alzheimer disease.

This study will evaluate the efficacy of intravenous immunoglobulin in patients with MCI over 24 months after the first infusion. This study will also document conversion from MCI to Alzheimer's Disease.


Condition Intervention Phase
Mild Cognitive Impairment
Drug: NewGam 10% IVIG
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blinded Placebo-Controlled Exploratory Study of Intravenous Immunoglobulin (NewGam 10%) in Amnestic Mild Cognitive Impairment

Resource links provided by NLM:


Further study details as provided by Sutter Health:

Primary Outcome Measures:
  • Change in ventricular volumetric as measured by MRI [ Time Frame: Baseline and 24 month MRI evaluation ] [ Designated as safety issue: No ]
    Change in ventricular volumetric as measured by MRI at baseline and 24 months following the first infusion of either 0.4 g/kg NewGam or 0.9% saline solution(placebo) every 14 days x 5


Secondary Outcome Measures:
  • Conversion from amnestic mild cognitive impairment (a-MCI) to Alzheimer Disease (AD) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    The National Institute of Neurological and Communicative Disorders and Stroke - Alzheimers Disease and Related Disorders Association (NINCDS-ADRDA) Alzheimer's Criteria were proposed in 1984 by NINCDS-ADRDA criteria for diagnosing Alzheimer Disease and Clinical Dementia Rating (CDR) will be used to determine conversion from a-MCI to AD.

  • Change in ventricular volume in patients with positive cerebrospinal fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer signature [ Time Frame: Baseline and 24 months following infusion ] [ Designated as safety issue: No ]
    MRI assessment at baseline and 24 months following infusion

  • Change in cognitive performance [ Time Frame: Baseline and 4, 8, 12, 16, 20, and 24 months after the first infusion ] [ Designated as safety issue: No ]

    Change in cognitive performance is measured by:

    • Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog)
    • Mini Mental State Exam (MMSE)
    • Clinical Dementia Rating (CDR) and Sum of Boxes (CDR-SB)


Estimated Enrollment: 50
Study Start Date: January 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: intravenous immunoglobulin (IVIG)
IVIG (NewGam 10%)at 0.4 g/kg
Drug: NewGam 10% IVIG

Subjects will be randomized to receive either an infusion of IVIG at 0.4 g/kg or 0.9% saline solution (placebo) every 14 days for two months for a total of five infusions.

Fifty subjects will be enrolled and randomized in a 1:1 IVIG 2.0 g/kg: placebo ratio. Twenty-five subjects will receive IVIG and 25 subjects will receive placebo.

Placebo Comparator: Saline solution
0.9% saline solution
Drug: NewGam 10% IVIG

Subjects will be randomized to receive either an infusion of IVIG at 0.4 g/kg or 0.9% saline solution (placebo) every 14 days for two months for a total of five infusions.

Fifty subjects will be enrolled and randomized in a 1:1 IVIG 2.0 g/kg: placebo ratio. Twenty-five subjects will receive IVIG and 25 subjects will receive placebo.


Detailed Description:

Screening procedures at visit 1 will take place up to 28 days prior to Visit 2 (Day 1) dosing. Screening labs and assessments will be performed during the screening period. A brain MRI will be obtained as standard of care within 6 months prior to the screening period. The first dose of study drug is administered on Day 1. Visits 2 through 6 have a ±1 day window and occur every 14 days over two months. The investigator will determine if a subject is suitable to continue following the missed infusion. Visits 7 through 12 (Month 4 through Month 24) have a ±7 day window.

All study screening data from Visit 1 including laboratory results must be reviewed for study eligibility prior to receiving first dose of study drug. Visit 2 physical exams and neurological exams prior to infusion may occur within 72 hours prior to the first infusion. Prior to infusion, a review of concomitant medications and adverse events takes place to ensure that no excluded medications have been added or medication discontinued or dose changed that were required to have been stable. If the subject continues to be eligible for enrollment, the subject will be randomized, infused with study medication and will remain in the infusion clinic for at least 4 hours following the start of the infusion for safety assessments on Visit 2 (Day 1).

  Eligibility

Ages Eligible for Study:   50 Years to 84 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age from 50 to < 85 years old.
  2. Diagnosis of Mild Cognitive Impairment, Amnestic type (single or multi domain) according to Petersen criteria (Appendix B) and supported by a CDR score of 0.5.
  3. Mini-Mental State Examination (MMSE) score of 24-30, inclusive.
  4. Rosen Modified Hachinski Ischemic score ≤ 4.
  5. Willing to consent to Apolipoprotein E (ApoE) testing and agree to disclose Apolipoprotein E4 (ApoE4) status. Previous ApoE testing will be accepted.
  6. Receiving stable doses of medication(s) for the treatment of non-excluded medical condition(s) for at least 30 days prior to screening.
  7. Ability to attend all clinical visits and have an informant capable of accompanying the subject on specific clinic visits for two years or the duration of the study.
  8. The subject's collaborative informant (support person) must be someone who has known the subject for at least 4 years; agrees to have at least 2 separate communications with the study participant per month for the duration of the study (one of these communications must be in person); and attends and completes the CDR interview at 8 study visits along with the subject.
  9. Fluency in English and evidence of adequate premorbid intellectual functioning.
  10. Adequate manual dexterity, visual, and auditory abilities to perform all aspects of the cognitive and functional assessments.
  11. Venous access suitable for repeated infusion and phlebotomy.

Exclusion criteria:

  1. Has significant neurological disease, other than a-MCI that may affect cognition.
  2. History of clinically evident stroke or history of clinically significant carotid or vertebrobasilar stenosis or plaque.
  3. History of seizures, excluding febrile seizures in childhood.
  4. Brain MRI shows moderate or severe cortical or hippocampal atrophy.
  5. Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, CSF shunts, claustrophobia, metal fragments or foreign objects in the eyes, skin, or body that would contraindicate a brain MRI scan.
  6. Current presence of a clinically significant major psychiatric disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR).
  7. History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma, and squamous cell carcinoma of the skin.
  8. Uncontrolled hypertension (diastolic BP> 100 mmHg or systolic BP> 160 mmHg, sitting).
  9. History or evidence of any clinically significant autoimmune disease or disorder of the immune system (eg., Crohn's Disease, Rheumatoid Arthritis)
  10. Women of childbearing potential.
  11. Weight greater than 120 kg (264 lbs).
  12. Excessive smoking defined as more than 20 cigarettes per day.
  13. History of alcohol or drug dependence or abuse as defined by DSM-IV criteria within the last 2 years.
  14. Severe liver or kidney disease verified by the PI review of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine.
  15. Known coagulopathy, thrombosis, or low platelet count.
  16. Known deficiency to Immunoglobulin A (IgA).
  17. Positive serology for Hepatitis B or C, or HIV.
  18. Concurrent or prior treatment with cholinesterase inhibitors and/or memantine, or Axona for cognitive enhancement. Exceptions (e.g. brief exposure to one of these medications) may be authorized if agreed upon by PI and sub-I.
  19. Concurrent use of anticholinergic drugs including diphenhydramine.
  20. Current use of anticonvulsant drugs for seizures, antiparkinson drugs, anticoagulant medications (except the use of aspirin 325 mg/day or less, plavix, aggrenox, and persantine but not for stroke).
  21. Concurrent use of opioid pain relievers and related synthetic derivatives.
  22. Use of experimental medications for AD or any other investigational medications or devices within 60 days prior to screening or within 5 half-lives of use of such a medication prior to screening, whichever is longer.
  23. Prior treatment with IVIG or other experimental immunotherapeutic or vaccine for MCI or AD, or prior treatment with a biological product for the treatment of a-MCI or AD.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01300728

Locations
United States, California
Sutter Neuroscience Medical Group
Sacramento, California, United States, 95816
Sponsors and Collaborators
Sutter Health
Investigators
Principal Investigator: Shawn Kile, M.D. Sutter Health
  More Information

Publications:
Responsible Party: Shawn Kile, M.D., MD, Sutter Health
ClinicalTrials.gov Identifier: NCT01300728     History of Changes
Other Study ID Numbers: IVIG-KILE-032010
Study First Received: February 22, 2011
Last Updated: December 12, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Sutter Health:
Intravenous immunotherapy
Conversion to Alzheimer Disease

Additional relevant MeSH terms:
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Immunoglobulins
Antibodies
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014