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

NCT02878538 | Withdrawn Early Phase 1 DMC FDA Drug

• 2 other identifiers: P30AG044271HSC20160395H
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• 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

  12 months

Secondary Outcomes (1)

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

  12 months

Study Arms (2)

deferiprone

ACTIVE COMPARATOR

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

Placebo Phase

PLACEBO COMPARATOR

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

Interventions

Deferiprone DRUG

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).

Also known as: Ferriprox, ATC Code V03AC02

deferiprone

Placebo phase OTHER

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

Placebo Phase

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

Related Publications (13)

• Becerril-Ortega J, Bordji K, Freret T, Rush T, Buisson A. Iron overload accelerates neuronal amyloid-beta production and cognitive impairment in transgenic mice model of Alzheimer's disease. Neurobiol Aging. 2014 Oct;35(10):2288-301. doi: 10.1016/j.neurobiolaging.2014.04.019. Epub 2014 May 1.

  PMID: 24863668 BACKGROUND

• De Chiara G, Marcocci ME, Sgarbanti R, Civitelli L, Ripoli C, Piacentini R, Garaci E, Grassi C, Palamara AT. Infectious agents and neurodegeneration. Mol Neurobiol. 2012 Dec;46(3):614-38. doi: 10.1007/s12035-012-8320-7. Epub 2012 Aug 17.

  PMID: 22899188 BACKGROUND

• 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.

  PMID: 25445365 BACKGROUND

• Gavett BE, Vudy V, Jeffrey M, John SE, Gurnani AS, Adams JW. The delta latent dementia phenotype in the uniform data set: Cross-validation and extension. Neuropsychology. 2015 May;29(3):344-52. doi: 10.1037/neu0000128. Epub 2014 Aug 25.

  PMID: 25151112 BACKGROUND

• 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.

  PMID: 7104545 BACKGROUND

• Nairz M, Schroll A, Sonnweber T, Weiss G. The struggle for iron - a metal at the host-pathogen interface. Cell Microbiol. 2010 Dec;12(12):1691-702. doi: 10.1111/j.1462-5822.2010.01529.x. Epub 2010 Oct 21.

  PMID: 20964797 BACKGROUND

• Peters DG, Connor JR, Meadowcroft MD. The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin. Neurobiol Dis. 2015 Sep;81:49-65. doi: 10.1016/j.nbd.2015.08.007. Epub 2015 Aug 22.

  PMID: 26303889 BACKGROUND

• Royall DR, Palmer RF, Markides KS. Exportation and Validation of Latent Constructs for Dementia Case Finding in a Mexican American Population-based Cohort. J Gerontol B Psychol Sci Soc Sci. 2017 Oct 1;72(6):947-955. doi: 10.1093/geronb/gbw004.

  PMID: 26968639 BACKGROUND

• Royall DR, Palmer RF; Texas Alzheimer's Research and Care. Validation of a latent construct for dementia case-finding in Mexican-Americans. J Alzheimers Dis. 2013;37(1):89-97. doi: 10.3233/JAD-130353.

  PMID: 23800829 BACKGROUND

• Royall DR, Palmer RF. Ethnicity moderates dementia's biomarkers. J Alzheimers Dis. 2015;43(1):275-87. doi: 10.3233/JAD-140264.

  PMID: 25079802 BACKGROUND

• Royall DR, Palmer RF. Thrombopoietin is associated with delta's intercept, and only in Non-Hispanic Whites. Alzheimers Dement (Amst). 2016 Feb 26;3:35-42. doi: 10.1016/j.dadm.2016.02.003. eCollection 2016.

  PMID: 27239547 BACKGROUND

• Royall DR, Palmer RF, O'Bryant SE; Texas Alzheimer's Research and Care Consortium. Validation of a latent variable representing the dementing process. J Alzheimers Dis. 2012;30(3):639-49. doi: 10.3233/JAD-2012-120055.

  PMID: 22451315 BACKGROUND

• Salkovic-Petrisic M, Knezovic A, Osmanovic-Barilar J, Smailovic U, Trkulja V, Riederer P, Amit T, Mandel S, Youdim MB. Multi-target iron-chelators improve memory loss in a rat model of sporadic Alzheimer's disease. Life Sci. 2015 Sep 1;136:108-19. doi: 10.1016/j.lfs.2015.06.026. Epub 2015 Jul 6.

  PMID: 26159898 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Deferiprone

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2016
• First Posted: August 25, 2016
• Study Start: January 1, 2018
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2023
• Last Updated: February 6, 2018

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)