Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201310000635418 Date of Registration: 30/08/2013
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Li in HAND RCT
Official scientific title A randomised controlled trial of lithium carbonate in individuals with HIV clade C-associated neurocognitive impairment: a phase IIb proof of principle study.
Brief summary describing the background and objectives of the trial Although ART improves neurological function in most patients with HAND, responses are often partial and progressive neurological disease may occur despite ART. There is a need to identify effective adjunctive treatments. The aim of the study is to determine the efficacy, safety and tolerability of lithium when given to HIV-infected patients stable on ART with neurocognitive impairment.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Li in HAND RCT
Disease(s) or condition(s) being studied Infections and Infestations,Mental and Behavioural Disorders,Nervous System Diseases
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 02/09/2013
Actual trial start date 08/10/2013
Anticipated date of last follow up 31/10/2014
Actual Last follow-up date 30/06/2015
Anticipated target sample size (number of participants) 108
Actual target sample size (number of participants) 66
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
20130318 MCC
M13\07\027 SU HREC
071/2013 UCT HREC
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Block randomisation (4, 6 or 8) Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Lithium carbonate 20mg/kg/day 24 weeks Dose of lithium will be titrated according to drug monitoring and adverse events 54 Placebo
Control Group Placebo 20mg/kg/day 24 weeks Dose of placebo will be titrated according to drug monitoring and adverse events 54
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Able to provide written informed consent. 2. HIV-infected male and female participant between 18 and 70 years (inclusive). 3. Currently on ART for at least 6 months. 4. Virologically suppressed on ART. 5. Cognitive impairment. 6. Female participants must have a negative pregnancy test and not be breastfeeding. 7. Females of child-bearing potential must commit to use of contraceptive methods with a failure rate of < 1% per year for the duration of the study. 8. Females not using an acceptable form of contraception must be of non-childbearing potential, surgically sterilized or post-menopausal. 1. Received an investigational drug within 30 days before the first dose of lithium carbonate. 2. Evidence of an active acquired immune deficiency syndrome (AIDS)-defining opportunistic infection within 30 days before the first dose of lithium carbonate. 3. History of drug or alcohol abuse within 3 months before screening. 4. Positive urine drug screen for drugs of abuse at screening. 5. Confirmed neurosyphilis. 6. Confirmed vitamin B12 deficiency. 7. Imaging structural abnormalities. 8. Neuropsychiatric disorders or serious psychiatric symptoms. 9. QTc greater than 450 msec for males and 470 msec for females. 10. Confirmed epilepsy on chronic treatment. 11. Use of any medications that may predispose the participant to lithium toxicity. 12. Clinically significant hypo- or hyperthyroidism. 13. Clinically significant hypercalcaemia or hypermagnesaemia. 14. Renal impairment. 15. Current diarrhoea and dehydration. 18 Year(s) 70 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/05/2013 University of Cape Town Human Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Room E52-24; Groote Schuur Hospital; Old Main Building; Observatory; 7925 CAPE TOWN 7925 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 11/02/2014 Stellenbosch University Health Research Ethics Committees (Human Research)
Ethics Committee Address
Street address City Postal code Country
Francie van Zijl Drive CAPE TOWN 7505 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To measure the change in neuropsychological function as determined by the Global Deficit Score (GDS) from baseline to week 24. Baseline & week 24
Secondary Outcome To measure changes in magnetic resonance spectroscopy (MRS)-based (glutamate and glutamine) Glx in the frontal grey matter and measures of tensor diffusivity (including fractional anisotropy, and radial, axial and mean diffusivity) in white matter from baseline to week 24. Baseline & week 24
Secondary Outcome To assess the severity and frequency of adverse events. Baseline & week 24
Secondary Outcome To measure changes in Human immunodeficiency virus (HIV) viral load in the plasma and cerebrospinal fluid (CSF). Baseline & week 24
Secondary Outcome To measure changes in CSF:serum albumin ratio. Baseline & week 24
Secondary Outcome To measure changes in CSF:serum viral load ratio. Baseline & week 24
Secondary Outcome To measure changes in glycogen synthase kinase-3-beta (GSK-3-ß) in human peripheral blood mononuclear cells (PBMC). Baseline & week 24
Secondary Outcome To study the effect of lithium on CSF dopamine and peripheral lymphocytes expressing dopamine receptors. Baseline & week 24
Secondary Outcome To study the effect of lithium brain-derived neurotrophic factor (BDNF) in serum and CSF. Baseline & week 24
Secondary Outcome To explore outcome measure potential associations with putative biomarkers, inflammatory markers or genes that might be identified during the course of the study. Baseline & week 24
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Groote Schuur Hospital Anzio Road Observatory 7950 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
European & Developing Countries Clinical Trials Partnership (EDCTP)
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Cape Town Bremner Building, Lovers Walk Rondebosch 7700 South Africa University
COLLABORATORS
Name Street address City Postal code Country
John Joska Div Neuropsychiatry, UCT, J Building, Groote Schuur Hospital, Anzio Rd Observatroy 7925 South Africa
Eric Decloedt Div Clinical Pharmacology, 7th Floor, Clinical Bldng, Faculty of Medicina and Health Sciences, Stellenbosch University Tygerberg 7505 South Africa
Gary Maartens Div Clinical Pharmacology, UCT, K$% Old Main Bldng, Groote Schuur Hospital, Anzio Rd Observatory 7925 South Africa
Simon Lovestone Institute of Psychiatry, M1,12, Main Wing, De Crespigny Park London SE5 8AF United Kingdom
Eleni Koutsillieri Univ Wurzburg, Instit Virology, Versbacherstrasse 7 Wuerzburg 97078 Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator John Joska john.joska@uct.ac.za +27 21 404 2154 Div Neuropsychiatry, UCT, J Building, Groote Schuur Hospital, Anzio Rd
City Postal code Country Position/Affiliation
Observatory 7925 South Africa
Role Name Email Phone Street address
Public Enquiries Eric Decloedt ericdecloedt@sun.ac.za +27 21 938 9340 Div Clinical Pharmacology, 7th Floor Clinical Bldng, Faculty of Medicine and Health Sciences, Stellenbosch University
City Postal code Country Position/Affiliation
Tygerberg 7505 South Africa
Role Name Email Phone Street address
Scientific Enquiries Eric Decloedt ericdecloedt@sun.ac.za +27 21 938 9340 Div Clinical Pharmacology, 7th Floor Clinical Bldng, Faculty of Medicine and Health Sciences, Stellenbosch University
City Postal code Country Position/Affiliation
Tygerberg 7505 South Africa
REPORTING
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