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A Pilot of the Feasibility of Using the Iron-Chelator Deferiprone on Mild Cognitive Impairment

Sponsor
The University of Texas Health Science Center at San Antonio (Other)
Overall Status
Withdrawn
CT.gov ID
NCT02878538
Collaborator
(none)
0
Enrollment
1
Location
2
Arms
62.9
Anticipated Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators propose to conduct a series of N of One (No1) single blinded clinical trials to pilot the feasibility of using the iron-chelator deferiprone on Mild Cognitive Impairment (MCI). Chelation therapy has previously been reported to slow the rate of cognitive decline in Alzheimer's Disease (AD) by 50% in a single human randomized clinical trial.

Condition or Disease Intervention/Treatment Phase
Early Phase 1

Detailed Description

Iron chelation's mechanism of action (MOA) in Alzheimer's disease (AD) is uncertain. Potential MOA include reversal of aluminum (AL) toxicity, the prevention of a-beta aggregation, β-amyloid disaggregation, and the obstruction of microbacterial and viral parasitism. The latter mechanism involves augmentation of innate immunity, and disruption of microbacterial iron metabolism. Infectious models of AD's pathophysiology have been recently proposed. Iron blocks toll-like receptor (TLR) initiated anti-microbial actions mediated via gamma-interferon (IFN-γ) tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10 (IL-10). These biomarkers are of interest because they have also been associated with our novel latent dementia phenotype (i.e., "d" for "dementia") in the Texas Alzheimer's Research and Care Consortium (TARCC). "d" is a continuous measure of dementia severity that can be constructed from any cognitive battery that also includes a measure of Instrumental Activities of Daily Living (IADL). Serum biomarkers might "trigger" dementing processes without participating in their later stages. Thus, the investigators have indications as to who might benefit from iron-chelation and when the intervention might be best applied. This knowledge may help them detect an effect of deferiprone on prospective change in "d" and even on MCI conversion in TARCC NHW (Non Hispanic White) subjects.

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Non-Randomized
Intervention Model:
Crossover Assignment
Masking:
Single (Participant)
Primary Purpose:
Other
Official Title:
An N of One Clinical Trial to Pilot the Feasibility of Using the Iron-Chelator Deferiprone on Mild Cognitive Impairment
Anticipated Study Start Date :
Jan 1, 2018
Anticipated Primary Completion Date :
Apr 1, 2022
Anticipated Study Completion Date :
Apr 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: deferiprone

Deferiprone will be administered three times a day (25mg/kg). Total dose per day will depend on participants' body weight for one, three month block.

Drug: Deferiprone
Subjects will then begin an experimental No1 design: placebo-deferiprone-placebo. Study drug will be administered in three 3 month blocks. All subjects will receive 30 days of active study drug. The placebo-deferiprone contrast compares placebo to active drug initiation. The deferiprone-placebo contrast tests active drug withdrawal. All will be given placebo in months 1-3, and 6-12. This will allow the investigators to examine active drug exposure on d score up to one year and prospective time to MCI conversion. Dosing: Participants will be treated 25 mg/kg po tid (75mg /kg /d total) The dose will be rounded by the prescriber to the nearest 250 mg (half-tablet).
Other Names:
  • Ferriprox, ATC Code V03AC02

    		•
    Placebo Comparator: Placebo Phase

    Placebo tablets with inactive substance will be used. Total number of placebo tablets will be equivalent to the active tablets administered depending on participants' body weight for two, three month blocks.

    Other: Placebo phase
    Placebo tablets with inactive substance will be provided to subjects for two, 3 month blocks during the study.

    Outcome Measures

    Primary Outcome Measures

    1. Efficacy of deferiprone therapy on "d" scores in Mild Cognitive Impairment (MCI) [12 months]

      Using N of 1 trial design in small number of MCI cases to compare within subject response to placebo and deferiprone in a A1-A-A1 design

    Secondary Outcome Measures

    1. Explore deferiprone's longitudinal effect on "d" and dementia conversion [12 months]

      We want to survey the effect of deferiprone on "d" to see If serum biomarkers trigger dementing processes in non Hispanic whites and if deferiprone exposure in MCI may terminate progression and conversion to dementia.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    65 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. MA (Mexican Americans) or NHW TARCC participants with competent informants;

    2. TARCC diagnosis of "MCI" (any subtype);

    3. Incident MCI or conversion to MCI from control in the two previous TARCC waves;

    4. 65-80 yrs of age;

    5. Non-institutionalized level of care;

    6. Capacity to give informed consent

    7. GDS (Geriatric Depression Screen) score (15 item) ≤ 6;

    8. TARCC MMSE (Mini-Mental State Examination) ≥ 26 /30;

    9. HIS (Hachinski Ischemic Scale) ≤ 05/15;

    10. Most recent TARCC dEQ-score = 0 ± 0.25.

    Exclusion Criteria:

    1. A clinical diagnosis of "Diabetes Mellitus" and current treatment with insulin;

    2. A self-reported diagnosis of "Major Depression" (treatment with "antidepressants" not exclusionary);

    3. A history of psychosis, including visual hallucinations;

    4. History or treatment for Parkinson's, or tremor, or Rapid Eye Movement (REM) behavior disorder;

    5. History or treatment for atrial fibrillation;

    6. Treatment for cancer in the last 5 years (exc. skin cancers);

    7. Major surgery in the last year;

    8. History of craniotomy;

    9. Serum Ferritin < 500mcg/ml, Hgb < 14g/dl♂ /12g/dl♀,, HCT < 45%♂ /40%♀, recent blood transfusion (last 5 years), FeSO4 supplementation, erythromycin therapy;

    10. ANC (absolute neutrophil count) < 500 cells/µL, platelet count < 150 × 106 /ml;

    11. Treatment with anti-convulsants, mood stabilizers, neuroleptics, opiates, muscle relaxants, systemic steroids, or AD-indicated agents.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Texas Health Science Center San Antonio Texas United States 78229

    Sponsors and Collaborators

    • The University of Texas Health Science Center at San Antonio

    Investigators

    • Principal Investigator: Donald R Royall, MD, The University of Texas Health Science Center at San Antonio
    • Principal Investigator: Dean Kellogg, MD, PHD, The University of Texas Health Science Center at San Antonio

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    The University of Texas Health Science Center at San Antonio
    ClinicalTrials.gov Identifier:
    NCT02878538
    Other Study ID Numbers:
    • P30AG044271
    • HSC20160395H
    First Posted:
    Aug 25, 2016
    Last Update Posted:
    Feb 6, 2018
    Last Verified:
    Aug 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Cognitive Dysfunction
    Deferiprone

    Study Results

    No Results Posted as of Feb 6, 2018