Neurocognitive DisturbancePhase 4NCT01348282
Efficacy and Safety of Two Pharmacologic Strategies on Neurocognitive Impairment in HIV Infection. The TRIANT-TE Study
A Phase 4 study testing Lithium and Rivastigmine in people with Neurocognitive Disturbance and HIV Infection, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 1 site in Spain.
Trial summary
The current project proposes the comparison of two pharmacologic strategies as adjunctive treatments for the improvement of HIV-associated neurocognitive disruption, additionally to use of HAART. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Neurocognitive Disturbance, HIV Infection
- What is being tested?
- Lithium and Rivastigmine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteSpain
- Study dates
- May 2011to Mar 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ranged from 20 to 75 years old
- Correct understanding of study objectives
- Written consent signed
- HIV infection confirmed by Western Blot or two ELISA tests
- Existence of an HIV-associated neurocognitive disorder according to the diagnosis classification offered by Antinori and cols (Neurology, 2007)
- Being on antiretroviral treatment.
- Spanish/Catalan speaker.
Who cannot join
- To be on a treatment that may interact pharmacologically with any of the new drugs used in study arms.
- Breastfeeding, pregnancy or fertile women willing to be pregnant.
- Renal failure or severe cardiovascular disease.
- Weakness, dehydration or severe sodium depletion.
- Sick sinus syndrome or cardiac conduction disturbances (sinoatrial block or atrioventricular block).
- Active duodenal or gastric ulcer.
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- Urinary obstruction.
- Epilepsy.
- Chronic obstructive pulmonary disease (COPD).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exploratory Controlled Prospective Randomized Trial to Compare the Efficacy and Safety of Two Different Pharmacology Strategies on Neurocognitive Impairment in HIV Infection. The TRIANT-TE Study
The current project proposes the comparison of two pharmacologic strategies as adjunctive treatments for the improvement of HIV-associated neurocognitive disruption, additionally to use of HAART. The investigators propose the use of the compound that has shown greatest benefits in this context to date, the lithium, versus the use of a well-tolerated and promising drug in other pathologies with neurocognitive affectation, such as Alzheimer or Parkinson diseases, which is the rivastigmine. In those other diseases, this second compound has recently offered a good tolerability, but also benefits on attention, memory and other neurocognitive areas. Both study groups, patients on therapy with lithium and patients on therapy with rivastigmine, will be compared to a control group, which will not initiate any other treatment (therefore only continuing antiretroviral therapy). The investigators are aware that this proposal will offer new relevant data for the study of neurocognitive improvement in HIV infection, as well will allow a better knowledge of clinical management of HIV-infected patients with CNS disease, an aspect that is a common clinical concern today.
Read the detailed description
Adjunctive treatments based on neurocognitive improvement for HIV-infected patients with CNS disruption have consisted essentially of neurostimulant or neuroprotective treatments. Reports published to date have involved valproic acid, peptide T, CPI-1189, selegiline, memantine, minocycline and lithium. Regarding valproic acid, two trials have confirmed lack of benefit using this compound on HIV-associated neurocognitive decline. In case of peptide T, CPI-1189, selegiline, memantine and minocycline, although their potential mechanisms on brain follow different pathways, trend towards improvement on neurocognitive functioning has been observed. Nonetheless, results on those trials are particularly based on a short term and, moreover, mild connections with benefits on neurocognitive and functional measures have been established. The lithium has been the compound showing clearest benefits on this regard. Two reports have consistently demonstrated benefits on neurocognitive performance using this neuroprotective agent, both in patients with HIV and showing impairment previously. However, lithium is well known to be a drug not easily incorporated in routine practice, at least further than in a psychiatry context. In addition, adverse events related to their use are relatively frequent, and therefore clinical follow-up must be especially controlled. Besides, lithium concentrations are also a concerning aspect considering its use, and drug plasma levels are recommended to be performed throughout the therapy application.
For all these reasons, the current project proposes the comparison of two pharmacologic strategies as adjunctive treatments for the improvement of HIV-associated neurocognitive disruption, additionally to use of HAART. The investigators propose the use of the compound that has shown greatest benefits in this context to date, the lithium, versus the use of a well-tolerated and promising drug in other pathologies with neurocognitive affectation, such as Alzheimer or Parkinson diseases, which is the rivastigmine. In those other diseases, this second compound has recently offered a good tolerability, but also benefits on attention, memory and other neurocognitive areas. Furthermore, in the case of this project, rivastigmine is suggested to be used through a transdermal system patch, a fact that can provide suitability and comfortability with regard to the selected administration method. Both study groups, patients on therapy with lithium and patients on therapy with rivastigmine, will be compared to a control group, which will not initiate any other treatment (therefore only continuing antiretroviral therapy). The investigators are aware that this proposal will offer new relevant data for the study of neurocognitive improvement in HIV infection, as well will allow a better knowledge of clinical management of HIV-infected patients with CNS disease, an aspect that is a common clinical concern today.
- Conditions
- Neurocognitive Disturbance, HIV Infection
- Being tested
- Lithium, Rivastigmine
- Keywords
- Neurocognitive Impairment, Controlled Randomized Trial, Coadjunctive Treatments, Lithium; Rivastigmine, Antiretroviral Therapy, HIV Infection
- Medical subject headings
- Cognition Disorders, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
lithium, in tablets, beginning a 2-daily 400 mg dose, and changing further adjusting the dose according to drug levels in serum.
RivastigmineDrug
rivastigmine, in transdermal patch administration, beginning a once-daily 4.6 mg dose, and changing further increasing the dose up to once-daily 9.5 mg.
| Study group | Role | What they receive |
|---|---|---|
| Lithium | Experimental | Lithium group: Patients who will initiate therapy with lithium, in tablets, beginning a 2-daily 400 mg dose, and changing further adjusting the dose according to drug levels in serum. Receives: Drug: Lithium |
| Rivastigmine | Active comparator | rivastigmine, in transdermal patch administration, beginning a once-daily 4.6 mg dose, and changing further increasing the dose up to once-daily 9.5 mg. Receives: Drug: Rivastigmine |
| Control group | No intervention | Patients who will not initiate treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of persons with neurocognitive impairment in the different study groups
The main variable to consider is the existence of HIV-associated neurocognitive impairment. Therefore, the percentage of persons with neurocognitive impairment in different study groups will be the main variable that will report on the improvement associated with new treatments.
Measured: From screening to month 12
Secondary outcomes (5)
Adverse events associated with the initiation of therapy and toxicity parameters
Measured: Week 2, month 1, 3, 6, 9, 12
Emotional variables
Depression and anxiety symptoms will be assessed by HADS questionnaire.
Measured: Baseline, month 3, 6, 12.
Functional variables
A total of six scales assessing functional interference regarding activities of daily living, as well as self-reported neurocognitive functioning, will be measured.
Measured: Baseline, month 3, 6, 12.
Quality of life variables
Four dimensions concerning quality of life, evaluated by MOS-HIV questionnaire, and satisfaction scales, based on treatments and clinical status, will be evaluated.
Measured: Baseline, month 3, 6, 12.
Demographics
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2011 (estimated)
- Study startMay 2011
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurocognitive DisturbanceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01348282
- Sponsor's protocol ID
- TRIANT-TE
- Status last verified
- Mar 2014
- First submitted
- 18 Apr 2011
- Last updated
- 1 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Controlled Prospective Randomized Trial to Compare the Efficacy and Safety of Two Different Pharmacology Strategies on Neurocognitive Impairment in HIV Infection. The TRIANT-TE Study
- ClinicalTrials.gov ID
- NCT01348282
- Acronym / sponsor ID
- TRIANT-TE
- Conditions
- Neurocognitive Disturbance, HIV Infection
- Keywords
- Neurocognitive Impairment, Controlled Randomized Trial, Coadjunctive Treatments, Lithium; Rivastigmine, Antiretroviral Therapy, HIV Infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la CienciaUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 5 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current project proposes the comparison of two pharmacologic strategies as adjunctive treatments for the improvement of HIV-associated neurocognitive disruption, additionally to use of HAART. The investigators propose the use of the compound that has shown greatest benefits in this context to date, the lithium, versus the use of a well-tolerated and promising drug in other pathologies with neurocognitive affectation, such as Alzheimer or Parkinson diseases, which is the rivastigmine. In those other diseases, this second compound has recently offered a good tolerability, but also benefits on attention, memory and other neurocognitive areas. Both study groups, patients on therapy with lithium and patients on therapy with rivastigmine, will be compared to a control group, which will not initiate any other treatment (therefore only continuing antiretroviral therapy). The investigators are aware that this proposal will offer new relevant data for the study of neurocognitive improvement in HIV infection, as well will allow a better knowledge of clinical management of HIV-infected patients with CNS disease, an aspect that is a common clinical concern today.
Detailed description
Adjunctive treatments based on neurocognitive improvement for HIV-infected patients with CNS disruption have consisted essentially of neurostimulant or neuroprotective treatments. Reports published to date have involved valproic acid, peptide T, CPI-1189, selegiline, memantine, minocycline and lithium. Regarding valproic acid, two trials have confirmed lack of benefit using this compound on HIV-associated neurocognitive decline. In case of peptide T, CPI-1189, selegiline, memantine and minocycline, although their potential mechanisms on brain follow different pathways, trend towards improvement on neurocognitive functioning has been observed. Nonetheless, results on those trials are particularly based on a short term and, moreover, mild connections with benefits on neurocognitive and functional measures have been established. The lithium has been the compound showing clearest benefits on this regard. Two reports have consistently demonstrated benefits on neurocognitive performance using this neuroprotective agent, both in patients with HIV and showing impairment previously. However, lithium is well known to be a drug not easily incorporated in routine practice, at least further than in a psychiatry context. In addition, adverse events related to their use are relatively frequent, and therefore clinical follow-up must be especially controlled. Besides, lithium concentrations are also a concerning aspect considering its use, and drug plasma levels are recommended to be performed throughout the therapy application.
For all these reasons, the current project proposes the comparison of two pharmacologic strategies as adjunctive treatments for the improvement of HIV-associated neurocognitive disruption, additionally to use of HAART. The investigators propose the use of the compound that has shown greatest benefits in this context to date, the lithium, versus the use of a well-tolerated and promising drug in other pathologies with neurocognitive affectation, such as Alzheimer or Parkinson diseases, which is the rivastigmine. In those other diseases, this second compound has recently offered a good tolerability, but also benefits on attention, memory and other neurocognitive areas. Furthermore, in the case of this project, rivastigmine is suggested to be used through a transdermal system patch, a fact that can provide suitability and comfortability with regard to the selected administration method. Both study groups, patients on therapy with lithium and patients on therapy with rivastigmine, will be compared to a control group, which will not initiate any other treatment (therefore only continuing antiretroviral therapy). The investigators are aware that this proposal will offer new relevant data for the study of neurocognitive improvement in HIV infection, as well will allow a better knowledge of clinical management of HIV-infected patients with CNS disease, an aspect that is a common clinical concern today.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lithium | Experimental | Drug: LithiumLithium group: Patients who will initiate therapy with lithium, in tablets, beginning a 2-daily 400 mg dose, and changing further adjusting the dose according to drug levels in serum. |
| Rivastigmine | Active comparator | Drug: Rivastigminerivastigmine, in transdermal patch administration, beginning a once-daily 4.6 mg dose, and changing further increasing the dose up to once-daily 9.5 mg. |
| Control group | No intervention | –Patients who will not initiate treatment |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ranged from 20 to 75 years old
- Correct understanding of study objectives
- Written consent signed
- HIV infection confirmed by Western Blot or two ELISA tests
- Existence of an HIV-associated neurocognitive disorder according to the diagnosis classification offered by Antinori and cols (Neurology, 2007)
Key exclusion criteria (9 listed)
- To be on a treatment that may interact pharmacologically with any of the new drugs used in study arms.
- Breastfeeding, pregnancy or fertile women willing to be pregnant.
- Renal failure or severe cardiovascular disease.
- Weakness, dehydration or severe sodium depletion.
- Sick sinus syndrome or cardiac conduction disturbances (sinoatrial block or atrioventricular block).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithiumlithium, in tablets, beginning a 2-daily 400 mg dose, and changing further adjusting the dose according to drug levels in serum. | Drug | Lithium |
| Rivastigminerivastigmine, in transdermal patch administration, beginning a once-daily 4.6 mg dose, and changing further increasing the dose up to once-daily 9.5 mg. | Drug | Rivastigmine |
Primary outcome
Percentage of persons with neurocognitive impairment in the different study groups
Time frame: From screening to month 12
The main variable to consider is the existence of HIV-associated neurocognitive impairment. Therefore, the percentage of persons with neurocognitive impairment in different study groups will be the main variable that will report on the improvement associated with new treatments.
5 secondary outcomes
Adverse events associated with the initiation of therapy and toxicity parameters
Time frame: Week 2, month 1, 3, 6, 9, 12
Emotional variables
Time frame: Baseline, month 3, 6, 12.
Functional variables
Time frame: Baseline, month 3, 6, 12.
Quality of life variables
Time frame: Baseline, month 3, 6, 12.
Demographics
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lithium and Rivastigmine in people with Neurocognitive Disturbance and HIV Infection, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of persons with neurocognitive impairment in the different study groups (time frame: From screening to month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2014.