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Sleep and Cognition After Atripla to Stribild Switch

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ClinicalTrials.gov Identifier: NCT02283060
Recruitment Status : Unknown
Verified March 2016 by University of Hawaii.
Recruitment status was:  Recruiting
First Posted : November 5, 2014
Last Update Posted : March 14, 2016
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
University of Hawaii

Brief Summary:

Atripla and Stribild are two FDA-Approved one pill a day combination antiretroviral medications given for the treatment of HIV. Both drugs are reasonably well tolerated. However, efavirenz, a component of Atripla, is known to cause "mental" side effects.

This proposal aims to assess whether a switch from Atripla to Stribild for 12 weeks will be associated with reversal of sleep and cognitive disturbances. Demonstrating changes upon withdrawal of drug and substitution of a drug regimen not known to have an impact on sleep and cognition may represent the best option to determine whether use of efavirenz is associated with effects on sleep and cognition beyond the immediate period following initiation of drug.


Condition or disease Intervention/treatment Phase
HIV Drug: Stribild Drug: Atripla Phase 4

Detailed Description:

Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) and Stribild (elvitegravir/emtricitabine/tenofovir disoproxil fumarate/cobicistat) are 2 FDA-approved 'one pill once a day' combination antiretroviral medications given for the treatment of HIV. Both have a common nucleoside reverse transcriptase inhibitor (NRTI) backbone of tenofovir (TDF) and emtricitabine (FTC), but differ in the 3rd medication contained in the pill. Atripla contains a non-nucleoside reverse transcriptase (NNRTI) drug efavirenz (EFV) while Stribild (elvitegravir/emtricitabine/tenofovir disoproxil fumarate/cobicistat) contains an integrase inhibitor elvitegravir with the drug cobicistat inactive against HIV but designed to simply boost the level of elvitegravir.

Both drugs are reasonable well tolerated. However, efavirenz is known to cause 'mental' side-effects. It is known that the initial use of EFV is associated with central nervous system (CNS) toxicity. The symptoms of such toxicity include daytime sleepiness, or alternatively inability to sleep, as well as vivid dreams including nightmares. The majority of such symptoms are believed to resolve within weeks; however there is controversy as to whether residual problems persist on a long term basis. Furthermore there are now reports of long time cognitive dysfunction associated with the use of efavirenz. Whether this is related to sleep disturbance is not clear. Studies to assess this impact have primarily involved assessment of sleep and cognitive function in antiretroviral (ART)-naïve subjects as they are initiated on first time ART that includes EFV. Such studies however are confounded by a 'return to health' phenomena as HIV per se is known to cause sleep and cognitive deficits . There is controversy regarding whether use of efavirenz leads to long term disturbances in sleep and cognition. HIV per se causes sleep and cognitive deficits6 and studies which have tried to assess problems in antiretroviral-naïve subject's pre- and post- initiation of efavirenz-based regimens may be confounded by a 'return to health' phenomena.

This proposal aims to assess whether a switch from efavirenz/emtricitabine/tenofovir disoproxil fumarate to elvitegravir/emtricitabine/tenofovir disoproxil fumarate/cobicistat will be associated with reversal of sleep and cognitive disturbances. Demonstrating changes upon withdrawal of drug and substitution of a drug regimen not known to have an impact on sleep or cognition may represent the best option to determine whether use of EFV is associated with effects on sleep and cognition beyond the immediate period following initiation of drug.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Change in Sleep Architecture and Neuropsychological Performance Following Switch From Atripla to Stribild.
Study Start Date : September 2014
Estimated Primary Completion Date : July 2016
Estimated Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Atripla

Arm Intervention/treatment
Experimental: Stribild switch arm
Patient to be taken off Atripla and switched to Stribild (co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) -one tablet taken daily with food
Drug: Stribild
To be administered orally, once daily with food.
Other Name: Co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate

Active Comparator: Atripla control arm
Patient to continue taking Atripla (co-formulated efavirenz/emtricitabine/ tenofovir disoproxil fumarate) - one tablet taken daily at bedtime on an empty stomach
Drug: Atripla
To be administered orally, once daily at bedtime on an empty stomach
Other Name: Co-formulated efavirenz/emtricitabine/ tenofovir disoproxil fumarate




Primary Outcome Measures :
  1. Change in sleep architecture assessed by formal sleep study [ Time Frame: 12 weeks ]
    Change in sleep architecture as assessed by formal sleep study

  2. Change in neuropsychological performance global and subdomain neuropsychological test scores [ Time Frame: 12 weeks ]
    Change in global and subdomain neuropsychological test scores


Secondary Outcome Measures :
  1. Change in Pittsburgh Sleep Quality Index Score [ Time Frame: 12 weeks ]
  2. Change in the frequency of use of sleep medications [ Time Frame: 12 weeks ]
  3. Change in the quality of life index score [ Time Frame: 12 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • HIV infected
  • Age 18 to 65 years
  • On stable efavirenz/emtricitabine/tenofovir disoproxil fumarate regimen > 12 months
  • Documented plasma HIV RNA < 50 copies/ml within 3 months of entry
  • Ability and willingness to provide written informed consent

Exclusion Criteria:

  • Receipt of any other antiretroviral drugs in addition to efavirenz/emtricitabine/tenofovir disoproxil fumarate within 6 months of study entry
  • Any documented plasma HIV RNA > 100 copies/ml within the past 6 months prior to study entry
  • Chronic hepatitis B as assessed by positive hepatitis B surface antigen [HBsAg]
  • Chronic hepatitis C as assessed by positive hepatitis C antibody [HCVab], except with proof of viral clearance and normal liver function tests
  • Other chronic disease which is uncontrolled or likely to interfere with study results
  • Acute illness within 2 weeks of entry
  • Previously documented history of OSA (obstructive sleep apnea)
  • Moderate to high risk of OSA defined as BMI (Body mass index) > 30 plus two of the following: habitual snoring, gasping/choking, observed apnea while sleeping, neck circumference > 17 inches
  • Severe depression based on the BDI-2 (Beck Depression Inventory - II)
  • Chronic daily receipt of medications associated with potential for sleep interference (i.e. psychoactive drugs, steroids, decongestants, beta blockers)
  • Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry.
  • Anticipated need for medications which are contraindicated as per Stribild package insert
  • Any known contra-indication to use of Stribild (elvitegravir/emtricitabine/tenofovir disoproxil fumarate/cobicistat)
  • Creatinine clearance (Cockcroft and Gault) < 70 ml/min
  • The following lab values:

    1. Hemoglobin < 9.0
    2. Absolute neutrophil count < 500/μL
    3. Platelet count < 40,000/μL
    4. AST (SGOT) and ALT (SGPT) > 5x ULN
  • Active or recent past history (within past 5 years) of illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with the protocol requirements
  • Pregnancy or breast-feeding, intent to become pregnant during the course of the study or breast-feeding
  • Patients, who, in the opinion of the Investigator, are unable to comply with the dosing schedule and protocol evaluation or for whom the study may not be advisable

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02283060


Contacts
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Contact: Lorna Nagamine, RN 808-692-1333 lornan@hawaii.edu

Locations
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United States, Hawaii
Hawaii Center for AIDS Recruiting
Honolulu, Hawaii, United States, 96813
Contact: Lorna Nagamine    808-692-1333    lornan@hawaii.edu   
Contact: Debbie Ogata-Arakaki    808-692-1332    ogataara@hawaii.edu   
Principal Investigator: Cecilia Shikuma, M.D.         
Sub-Investigator: Bruce Soll, M.D.         
Sub-Investigator: Dominic Chow, M.D., Ph.D.         
Sub-Investigator: Beau Nakamoto, M.D., Ph.D.         
Sub-Investigator: Kalpana Kallianpur, Ph.D.         
Sub-Investigator: Tracie Umaki, Psy.D.         
Sponsors and Collaborators
University of Hawaii
Gilead Sciences

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Responsible Party: University of Hawaii
ClinicalTrials.gov Identifier: NCT02283060     History of Changes
Other Study ID Numbers: H027
First Posted: November 5, 2014    Key Record Dates
Last Update Posted: March 14, 2016
Last Verified: March 2016

Keywords provided by University of Hawaii:
Atripla
Stribild
HIV
Sleep architecture
Neuropsychological performance

Additional relevant MeSH terms:
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Tenofovir
Emtricitabine
Efavirenz
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Cobicistat
Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 CYP3A Inhibitors