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

Primary Purpose

Mild Cognitive Impairment

Status

Withdrawn

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Deferiprone

Placebo phase

About this trial

This is an interventional other trial for Mild Cognitive Impairment

Eligibility Criteria

65 Years - 80 Years (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

MA (Mexican Americans) or NHW TARCC participants with competent informants;
TARCC diagnosis of "MCI" (any subtype);
Incident MCI or conversion to MCI from control in the two previous TARCC waves;
65-80 yrs of age;
Non-institutionalized level of care;
Capacity to give informed consent
GDS (Geriatric Depression Screen) score (15 item) ≤ 6;
TARCC MMSE (Mini-Mental State Examination) ≥ 26 /30;
HIS (Hachinski Ischemic Scale) ≤ 05/15;
Most recent TARCC dEQ-score = 0 ± 0.25.

Exclusion Criteria:

A clinical diagnosis of "Diabetes Mellitus" and current treatment with insulin;
A self-reported diagnosis of "Major Depression" (treatment with "antidepressants" not exclusionary);
A history of psychosis, including visual hallucinations;
History or treatment for Parkinson's, or tremor, or Rapid Eye Movement (REM) behavior disorder;
History or treatment for atrial fibrillation;
Treatment for cancer in the last 5 years (exc. skin cancers);
Major surgery in the last year;
History of craniotomy;
Serum Ferritin < 500mcg/ml, Hgb < 14g/dl♂ /12g/dl♀,, HCT < 45%♂ /40%♀, recent blood transfusion (last 5 years), FeSO4 supplementation, erythromycin therapy;
ANC (absolute neutrophil count) < 500 cells/µL, platelet count < 150 × 106 /ml;
Treatment with anti-convulsants, mood stabilizers, neuroleptics, opiates, muscle relaxants, systemic steroids, or AD-indicated agents.

Sites / Locations

University of Texas Health Science Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

deferiprone

Placebo Phase

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Efficacy of deferiprone therapy on "d" scores in Mild Cognitive Impairment (MCI)

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

Explore deferiprone's longitudinal effect on "d" and dementia conversion

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.

Full Information

NCT ID

NCT02878538

First Posted

August 5, 2016

Last Updated

February 5, 2018

Sponsor

The University of Texas Health Science Center at San Antonio

1. Study Identification

Unique Protocol Identification Number

NCT02878538

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Withdrawn

Why Stopped

Study was withdrawn before IRB approval

Study Start Date

January 2018 (Anticipated)

Primary Completion Date

April 2022 (Anticipated)

Study Completion Date

April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Texas Health Science Center at San Antonio

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mild Cognitive Impairment

7. Study Design

Primary Purpose

Other

Study Phase

Early Phase 1

Interventional Study Model

Crossover Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

deferiprone

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Placebo Phase

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Deferiprone

Other Intervention Name(s)

Ferriprox, ATC Code V03AC02

Intervention Description

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).

Intervention Type

Other

Intervention Name(s)

Placebo phase

Intervention Description

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

Primary Outcome Measure Information:

Title

Efficacy of deferiprone therapy on "d" scores in Mild Cognitive Impairment (MCI)

Description

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

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Explore deferiprone's longitudinal effect on "d" and dementia conversion

Description

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: MA (Mexican Americans) or NHW TARCC participants with competent informants; TARCC diagnosis of "MCI" (any subtype); Incident MCI or conversion to MCI from control in the two previous TARCC waves; 65-80 yrs of age; Non-institutionalized level of care; Capacity to give informed consent GDS (Geriatric Depression Screen) score (15 item) ≤ 6; TARCC MMSE (Mini-Mental State Examination) ≥ 26 /30; HIS (Hachinski Ischemic Scale) ≤ 05/15; Most recent TARCC dEQ-score = 0 ± 0.25. Exclusion Criteria: A clinical diagnosis of "Diabetes Mellitus" and current treatment with insulin; A self-reported diagnosis of "Major Depression" (treatment with "antidepressants" not exclusionary); A history of psychosis, including visual hallucinations; History or treatment for Parkinson's, or tremor, or Rapid Eye Movement (REM) behavior disorder; History or treatment for atrial fibrillation; Treatment for cancer in the last 5 years (exc. skin cancers); Major surgery in the last year; History of craniotomy; Serum Ferritin < 500mcg/ml, Hgb < 14g/dl♂ /12g/dl♀,, HCT < 45%♂ /40%♀, recent blood transfusion (last 5 years), FeSO4 supplementation, erythromycin therapy; ANC (absolute neutrophil count) < 500 cells/µL, platelet count < 150 × 106 /ml; Treatment with anti-convulsants, mood stabilizers, neuroleptics, opiates, muscle relaxants, systemic steroids, or AD-indicated agents.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Donald R Royall, MD

Organizational Affiliation

The University of Texas Health Science Center at San Antonio

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Dean Kellogg, MD, PHD

Organizational Affiliation

The University of Texas Health Science Center at San Antonio

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas Health Science Center

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24863668

Citation

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Results Reference

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22899188

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Citation

Fine JM, Renner DB, Forsberg AC, Cameron RA, Galick BT, Le C, Conway PM, Stroebel BM, Frey WH 2nd, Hanson LR. Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation. Neurosci Lett. 2015 Jan 1;584:362-7. doi: 10.1016/j.neulet.2014.11.013. Epub 2014 Nov 13.

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Citation

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PubMed Identifier

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Citation

Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982 Jun;140:566-72. doi: 10.1192/bjp.140.6.566.

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Citation

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PubMed Identifier

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Citation

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Citation

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Citation

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Citation

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Citation

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

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