Evaluation of Lithium as a Glycogen-Synthase-Kinase-3 (GSK-3) Inhibitor in Mild Cognitive Impairment

NCT02601859 | Completed

• 1 other identifier: 2014MH08
• Study Type: interventional
• Target: 11
• Locations: 0 countries
• Sites: N/A

Brief Summary

The project is designed to generate critical information to design and justify a robust trial on lithium prevention of the onset of Alzheimer's disease (AD). Lithium exerts and inhibitory effect on Glycogen synthase kinase 3 (GSK-3) a brain biomarker of neuroprotection. The study consists of 3 phases:

1. 1.Phase 1 investigates rats to establish a reliable method to measure brain biomarker activity levels from blood biomarker activity.
2. 2.Phase 2 will determine whether the GSK3 enzyme activity is significantly different in subjects with MCI compared to normal individuals.
3. 3.Phase 3 investigates patients with MCI taking lithium to establish the minimum lithium dose required to inhibit the activity of GSK-3.

Conditions

Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• GSK-3 activity in PBMC isolates

  Measures are six robust measures are of upstream/downstream signalling and GSK3 function and will be validated by other work by the investigators. GSK-3 function will be described according to plasma Lithium concentration.

  12 weeks

Study Arms (1)

Phase 3

EXPERIMENTAL

Administration of Lithium to 11 individuals with MCI (non-randomised) for 9 weeks. Lithium dose escalates from 100mg to 200mg to 400mg, then a 3 week wash out period, total study duration 12 weeks. Blood samples taken at regular intervals throughout trial and analysed for GSK-3 enzyme activity in blood.

Drug: Lithium Carbonate

Interventions

Lithium Carbonate DRUG

Phase 3

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of Mild Cognitive Impairment (MCI).

You may not qualify if:

• Previous hypersensitivity to Lithium or other contraindication to Lithium carbonate Priadel (see most recent SmPC), Dementia Diabetes BMI \<18 or \>30 Rheumatoid Arthritis and Autoimmune Inflammatory disorders Currently taking NSAIDS Moderate renal failure (defined in BNF by gGFR \<60 mL/minute/1.73m2) or severe Renal failure (defined in BNF by eGFR \<29 mL/minute/1.73m2 Addison's disease, Brugada syndrome (or family history of Brugada syndrome), cardiac insufficiency, congestive cardiac failure, epilepsy, suicidality incapacity to consent currently prescribed lithium participation in another clinical trial of an Investigational Medicinal Product (IMP) in the last 28 days.
• Uncontrolled serious concomitant physical illness

Sponsors & Collaborators

• University of Dundee: lead
• University of Oxford: collaborator

Related Publications (1)

• Duthie A, van Aalten L, MacDonald C, McNeilly A, Gallagher J, Geddes J, Lovestone S, Sutherland C. Recruitment, Retainment, and Biomarkers of Response; A Pilot Trial of Lithium in Humans With Mild Cognitive Impairment. Front Mol Neurosci. 2019 Jun 28;12:163. doi: 10.3389/fnmol.2019.00163. eCollection 2019.

  PMID: 31316348 RESULT

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2015
• First Posted: November 10, 2015
• Study Start: August 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: August 9, 2021

Record last verified: 2021-08