Clinical trial NCT01348282: Efficacy and Safety of Two Pharmacologic Strategies on Neurocognitive Impairment in HIV Infection. The TRIANT-TE 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neurocognitive Disturbance
HIV Infection
Keywords: Neurocognitive Impairment
Controlled Randomized Trial
Coadjunctive Treatments
Lithium; Rivastigmine
Antiretroviral Therapy
HIV Infection
Lead sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Sponsor class: OTHER
First posted: 2011-05-05
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Urinary obstruction.
* Epilepsy.
* Chronic obstructive pulmonary disease (COPD).

Primary outcomes:
measure: Percentage of persons with neurocognitive impairment in the different study groups
timeFrame: From screening to month 12
Secondary outcomes:
measure: Adverse events associated with the initiation of therapy and toxicity parameters
timeFrame: Week 2, month 1, 3, 6, 9, 12
measure: Emotional variables
timeFrame: Baseline, month 3, 6, 12.
measure: Functional variables
timeFrame: Baseline, month 3, 6, 12.
measure: Quality of life variables
timeFrame: Baseline, month 3, 6, 12.
measure: Demographics
timeFrame: Baseline
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Fundació LLuita contra la SIDA
state: Barcelona
Study officials:
References: