Efficacy and Safety of Two Pharmacologic Strategies on Neurocognitive Impairment in HIV Infection. The TRIANT-TE Study

NCT ID: NCT01348282

Last Updated: 2014-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2014-03-31

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.

Conditions

Neurocognitive Disturbance; HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lithium

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.

Group Type: EXPERIMENTAL

Lithium

Intervention Type: DRUG

lithium, in tablets, beginning a 2-daily 400 mg dose, and changing further adjusting the dose according to drug levels in serum.

Rivastigmine

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.

Group Type: ACTIVE_COMPARATOR

Rivastigmine

Intervention Type: DRUG

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.

Control group

Patients who will not initiate treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Lithium

lithium, in tablets, beginning a 2-daily 400 mg dose, and changing further adjusting the dose according to drug levels in serum.

Intervention Type: DRUG

Rivastigmine

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.

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Fundació LLuita contra la SIDA

Badalona, Barcelona, Spain

Countries

Spain

Other Identifiers

TRIANT-TE

Identifier Type: -

Identifier Source: org_study_id