ANZCTR - Registration

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12617001339347p

Ethics application status

Submitted, not yet approved

Date submitted

20/08/2017

Date registered

21/09/2017

Date last updated

25/07/2019

Date data sharing statement initially provided

20/11/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Effects of lithium and fampridine on electroencephalography profiles in healthy volunteers

Scientific title

Effects of lithium and fampridine on electroencephalography profiles in healthy volunteers

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Li 4AP EEG

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Bipolar Disorder

Condition category

Condition code

Mental Health

Depression

Mental Health

Other mental health disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Pilot study.
Participants will be assigned to one of 4 oral treatment groups: placebo, lithium (750mg), fampridine (1mg or 2mg).
Allocation to a treatment group will be carried out by a computer generated random code. Daily doses of one of the 4 treatments will be administered for 7 days.
On the first, second and last days of the study (before dosing, post single dose and post 1 week of dosing) participants will have a (10 minute) resting state EEG recorded.
Adherence will be monitored by checking participants' drug containers at the end of each dosing week, and also sending daily text messages to participants to remind them to take their study treatments.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

The placebo capsule will contain lactose.

Control group

Placebo

Outcomes

Primary outcome [1]

Composite primary outcome.
Statistically significant differences in activity in infraslow (<1Hz), delta (1-4Hz), theta (4-7
Hz), alpha (8-13Hz), beta (13-30Hz) and gamma (>30Hz) bands in EEG data in response to drug treatments (versus placebo control and normative EEG database).

Timepoint [1]

Baseline and end of treatment period

Primary outcome [2]

Composite primary outcome.
Statistically significant differences in functional connectivity in infraslow (<1Hz), delta (1-4Hz), theta (4-7
Hz), alpha (8-13Hz), beta (13-30Hz) and gamma (>30Hz) bands in EEG data in response to drug treatments (versus placebo control and normative EEG database).

Timepoint [2]

Baseline and end of treatment period

Secondary outcome [1]

Changes in visual analogue mood scale scores.
Self rated mood (happy, sad, calm, tense, energetic, sleepy) rated from 0 (not at all) to 100 (extremely)

Timepoint [1]

Immediately prior to EEG recording

Secondary outcome [2]

Safety and tolerability. Endpoints include: vital signs (blood pressure, heart rate), reported adverse events.

Timepoint [2]

Pre-dose to 3h post-dose (continuous) on clinic visit days.

Secondary outcome [3]

Pharmacokinetics of lithium and fampridine.
The pharmacokinetic parameter for lithium and fampridine is C2h (drug concentrations at the time the EEG is being recorded).
This is a composite secondary outcome.

Timepoint [3]

Two hours after dosing on treatment days when EEGs are performed (day 2 and day 8).

Eligibility

Key inclusion criteria

To be included in the study, participants must meet all of the following inclusion criteria:
1. Capable of understanding and signing an informed consent.
2. Aged >18 years on the day of consent.
3. Good general health.
4. Suitable venous access.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

To be included in the study, participants must meet none of the following exclusion criteria:
1. Females who are or intend to become pregnant, or are lactating.
2. Participants who, in the opinion of the investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved).
3. Any participant for whom the investigator believes, for any reason, that participation would not be an acceptable risk.
4. Regular use of any drug that alters mood or is used to treat mental disorder, including daily use of alcohol or use of alcohol within 24 hours of testing.
5. Subjects with a prior history of seizures; susceptibility to photosensitivity; or a history of allergic skin reactions.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Central randomisation by phone/fax/computer
Prof Glue will create the random codes. All study personnel involved with recruitment, dosing, data collection and analysis will have no access to the random codes until the databases are locked.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Allocation to blinded study treatment (placebo, lithium, fampridine) is by random code with administration sequence balanced, and includes gender as a stratification factor.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Crossover

Other design features

Phase

Phase 1

Type of endpoint/s

Pharmacokinetics / pharmacodynamics

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/08/2019

Actual

Date of last participant enrolment

Anticipated

20/12/2019

Actual

Date of last data collection

Anticipated

27/12/2019

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Otago

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Otago

Address [1]

PO Box 56
Dunedin, 9054

Country [1]

New Zealand

Primary sponsor type

University

Name

University of Otago

Address

PO Box 56
Dunedin, 9054

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

Northern A HDEC

Ethics committee address [1]

Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

01/03/2018

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Lithium is the first line treatment for bipolar disorder (BD), a disorder characterised by cyclic perturbations in mood, correlated with aberrant patterns of brain connectivity and rhythmicity in distributed brain networks. These patterns of activity, reflecting the intrinsic electrophysiological properties of constituent neurons, are dependent upon membrane ion channel function. BD is strongly associated with disturbances in genes responsible for ion channel expression, localisation and structure and can be treated with some antiepileptic drugs, acting directly on ion channels. Thus, ion channel dysfunction is strongly implicated in BD, however, lithium has had no known effect on ion channels.
Recently, we found that lithium selectively blocks a specific K+ current, the delay current (ID), found in several types of brain neuron. ID can influence action potential threshold and output timing, how inputs from different synaptic sources are integrated, and network synchrony and rhythmicity. Output timing (gating) and synchrony are important variables in brain network function, contributing to the formation and dissolution of functional brain networks over time. Modulation of ID, including by lithium, may influence patterns of connectivity and rhythmicity in the brain and could explain the effectiveness of lithium in BD.
We have found, additionally, that Fampridine (4AP), a prescription treatment for multiple sclerosis, blocks ID in cortical projection neurons in vitro. We therefore hypothesise, that Fampridine may act as an adjunctive or replacement therapy for lithium in BD. In order to assess this hypothesis, we aim to examine activity and functional connectivity changes in EEG recordings of healthy volunteers in the presence of lithium, Fampridine and placebo control.

The specific objectives of the study are:
•	To examine the early and late effects of dose (Fampridine) and dose timing of lithium and Fampridine on EEG changes in healthy volunteers.
•	To evaluate the magnitude and duration of affective changes following administration of lithium, Fampridine or placebo in healthy volunteers. Blood testing will also show any associations of cognitive changes with levels of Li+ / Fampridine and its metabolites in the participant’s bloodstream.

Trial website

None

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Paul Glue

Address

Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054

Country

New Zealand

Phone

+64 21 243 3372

Fax

[email protected]

Contact person for public queries

Name

Paul Glue

Address

Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054

Country

New Zealand

Phone

+64 3 4709451

Fax

[email protected]

Contact person for scientific queries

Name

Paul Glue

Address

Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054

Country

New Zealand

Phone

+64 21 243 3372

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically