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

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ClinicalTrials.gov Identifier: NCT02878538
Recruitment Status : Withdrawn (Study was withdrawn before IRB approval)
First Posted : August 25, 2016
Last Update Posted : February 6, 2018
Sponsor:
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

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
Mild Cognitive Impairment Drug: Deferiprone Other: Placebo 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.

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Study Type : Interventional  (Clinical Trial)
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
Estimated Study Start Date : January 2018
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Iron
Drug Information available for: Deferiprone

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 Name: 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.




Primary Outcome Measures :
  1. Efficacy of deferiprone therapy on "d" scores in Mild Cognitive Impairment (MCI) [ Time Frame: 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 [ Time Frame: 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.



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Ages Eligible for Study:   65 Years to 80 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02878538


Locations
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United States, Texas
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
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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
Publications:

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Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02878538    
Other Study ID Numbers: P30AG044271 ( U.S. NIH Grant/Contract )
HSC20160395H ( Other Identifier: University of Texas Health Science Center- San Antonio )
First Posted: August 25, 2016    Key Record Dates
Last Update Posted: February 6, 2018
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Deferiprone
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action