A Pilot Clinical Trial With the Iron Chelator Deferiprone in Parkinson's Disease

NCT01539837 | Completed Phase 2 Results DMC

• 3 other identifiers: ICL-11/SC/01012011-001148-3111/SC/0101
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Parkinson's disease (PD) is a common neurodegenerative disease affecting movement. Although drug treatments for PD are available they only treat the symptoms of the disease, fail to halt neuronal loss, and are associated with long term side effects and loss of efficacy. There is a chronic need to develop neuroprotective therapies. Increased iron and oxidative stress have been heavily implicated in the neurodegenerative process in PD, hence removal of excess iron by iron chelation represents a potential drug target. Iron chelators are extensively utilised to treat peripheral iron overload disorders (e.g. thalassaemia) and recently the investigators have demonstrated iron chelators such as Deferiprone can enter the brain removing excess iron and are neuroprotective in PD animal models. Although good tolerability and efficacy to remove brain iron has also been shown in a pilot study with the iron chelators Deferiprone in young patients with Friedreich Ataxia, where iron accumulates in the dentate nucleus, no studies have been conducted in aged individuals affected by PD. Hence the aims of this study are 1) to assess whether Deferiprone is well tolerated in PD patients, 2) whether Deferiprone can remove the excess iron levels found in the brain area affected by PD, the substantia nigra, as assessed by Magnetic resonance imaging (MRI) and 3) whether Deferiprone has any direct effect on the clinical symptoms of PD. Three groups of 12 (total 36) early stage drug free PD patients will be treated with 20 or 30mg/kg/d Deferiprone or Placebo for 6 months. Over the 6 months patients will receive serial MRI scans, neurological examinations not only to assess PD symptoms but also psychological state, plus blood test to monitor for potential side effects. Positive results from this pilot will help support larger clinical trials to evaluate whether Deferiprone can slow down/halt PD.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Brain Iron; Iron chelation; Oxidative stress

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Serious Adverse Events

  To assess whether there were any serious adverse events in 6-month treatment with Deferiprone.

  6 months

Secondary Outcomes (1)

• Iron Concentrations in the Dentate Nucleus

  6 months

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug excipient

Drug: Placebo

Deferiprone 20mg

ACTIVE COMPARATOR

20mg/kg/day deferiprone

Drug: Deferiprone 20mg

Deferiprone 30mg

ACTIVE COMPARATOR

30mg/kg/day Deferiprone

Drug: Deferiprone 30mg

Interventions

Deferiprone 20mg DRUG

20mg/kg/d Deferiprone divided into two equal doses (morning and evening), every day for 6 months

Also known as: Ferriprox

Deferiprone 20mg

Placebo DRUG

Feriprox placebo administered orally at the same dosing volume as the 20mg/kg/day feriprox per day

Also known as: Feriprox placebo

Placebo

Deferiprone 30mg DRUG

30mg/kg/d Deferiprone divided into two equal doses (morning and evening), every day for 6 months

Also known as: Ferriprox

Deferiprone 30mg

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of Parkinson's disease
• disease duration less than 5 years
• stable response to standard anti-Parkinson's medication for at least 6 weeks

You may not qualify if:

• Other neurological conditions
• Diabetes
• Renal or liver disease
• Blood disorders
• Pregnancy or breast feeding
• Conditions which cause immunocompromise e.g. episodes of neutropaenia or agranulocytosis, HIV etc
• Prior history of hypersensitivity to Deferiprone or its excipient
• Pacemaker
• artificial heart valves
• ever had surgery to the head
• Metalic implants in the CNS e.g. cerebral aneurysm clips
• history of metal entering the eye

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Centre for Neuroscience, Imperial College London

London, W120NN, United Kingdom

Location

Related Publications (6)

• Dexter DT, Wells FR, Agid F, Agid Y, Lees AJ, Jenner P, Marsden CD. Increased nigral iron content in postmortem parkinsonian brain. Lancet. 1987 Nov 21;2(8569):1219-20. doi: 10.1016/s0140-6736(87)91361-4. No abstract available.

  PMID: 2890848 BACKGROUND

• Oakley AE, Collingwood JF, Dobson J, Love G, Perrott HR, Edwardson JA, Elstner M, Morris CM. Individual dopaminergic neurons show raised iron levels in Parkinson disease. Neurology. 2007 May 22;68(21):1820-5. doi: 10.1212/01.wnl.0000262033.01945.9a.

  PMID: 17515544 BACKGROUND

• Ward RJ, Dexter D, Florence A, Aouad F, Hider R, Jenner P, Crichton RR. Brain iron in the ferrocene-loaded rat: its chelation and influence on dopamine metabolism. Biochem Pharmacol. 1995 Jun 16;49(12):1821-6. doi: 10.1016/0006-2952(94)00521-m.

  PMID: 7598744 BACKGROUND

• Dexter DT, Statton SA, Whitmore C, Freinbichler W, Weinberger P, Tipton KF, Della Corte L, Ward RJ, Crichton RR. Clinically available iron chelators induce neuroprotection in the 6-OHDA model of Parkinson's disease after peripheral administration. J Neural Transm (Vienna). 2011 Feb;118(2):223-31. doi: 10.1007/s00702-010-0531-3. Epub 2010 Dec 17.

  PMID: 21165659 BACKGROUND

• Boddaert N, Le Quan Sang KH, Rotig A, Leroy-Willig A, Gallet S, Brunelle F, Sidi D, Thalabard JC, Munnich A, Cabantchik ZI. Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood. 2007 Jul 1;110(1):401-8. doi: 10.1182/blood-2006-12-065433. Epub 2007 Mar 22.

  PMID: 17379741 BACKGROUND

• Martin-Bastida A, Ward RJ, Newbould R, Piccini P, Sharp D, Kabba C, Patel MC, Spino M, Connelly J, Tricta F, Crichton RR, Dexter DT. Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson's disease. Sci Rep. 2017 May 3;7(1):1398. doi: 10.1038/s41598-017-01402-2.

  PMID: 28469157 RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

Deferiprone

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: David Dexter
• Organization: Imperial College London

d.dexter@imperial.ac.uk

+44 (0)20 7594 6665

Study Officials

• David T Dexter, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2012
• First Posted: February 28, 2012
• Study Start: February 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 16, 2020
• Results First Posted: June 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)