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

February 5, 2018 updated by: The University of Texas Health Science Center at San Antonio

An N of One Clinical Trial to Pilot the Feasibility of Using the Iron-Chelator Deferiprone on Mild Cognitive Impairment

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years to 80 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2018

Primary Completion (Anticipated)

April 1, 2022

Study Completion (Anticipated)

April 1, 2023

Study Registration Dates

First Submitted

August 5, 2016

First Submitted That Met QC Criteria

August 19, 2016

First Posted (Estimate)

August 25, 2016

Study Record Updates

Last Update Posted (Actual)

February 6, 2018

Last Update Submitted That Met QC Criteria

February 5, 2018

Last Verified

August 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P30AG044271 (U.S. NIH Grant/Contract)
  • HSC20160395H (Other Identifier: University of Texas Health Science Center- San Antonio)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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