HIVPhase 4NCT02283060
Sleep and Cognition After Atripla to Stribild Switch
A Phase 4 study testing Stribild and Atripla in people with HIV, run by University of Hawaii at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV
- What is being tested?
- Stribild and Atripla
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Aug 2016
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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:
- Hemoglobin < 9.0
- Absolute neutrophil count < 500/μL
- Platelet count < 40,000/μL
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Hawaii Center for AIDS
Honolulu, Hawaii, 96813
Lorna Nagamine, 808-692-1333, lornan@hawaii.edu
Debbie Ogata-Arakaki, 808-692-1332, ogataara@hawaii.edu
About this study
Official title: Change in Sleep Architecture and Neuropsychological Performance Following Switch From Atripla to Stribild.
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.
Read the 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.
- Conditions
- HIV
- Being tested
- Stribild, Atripla
- Keywords
- Atripla, Stribild, HIV, Sleep architecture, Neuropsychological performance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
StribildDrug
Also called Co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
To be administered orally, once daily with food.
AtriplaDrug
Also called Co-formulated efavirenz/emtricitabine/ tenofovir disoproxil fumarate
To be administered orally, once daily at bedtime on an empty stomach
| Study group | Role | What they receive |
|---|---|---|
| Stribild switch arm | Experimental | Patient to be taken off Atripla and switched to Stribild (co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) -one tablet taken daily with food Receives: Drug: Stribild |
| Atripla control arm | Active comparator | Patient to continue taking Atripla (co-formulated efavirenz/emtricitabine/ tenofovir disoproxil fumarate) - one tablet taken daily at bedtime on an empty stomach Receives: Drug: Atripla |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in sleep architecture assessed by formal sleep study
Change in sleep architecture as assessed by formal sleep study
Measured: 12 weeks
Change in neuropsychological performance global and subdomain neuropsychological test scores
Change in global and subdomain neuropsychological test scores
Measured: 12 weeks
Secondary outcomes (3)
Change in Pittsburgh Sleep Quality Index Score
Measured: 12 weeks
Change in the frequency of use of sleep medications
Measured: 12 weeks
Change in the quality of life index score
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2014 (estimated)
- Study startSep 2014
- Primary completionJul 2016 (estimated)
- Study completionAug 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Hawaii
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02283060
- Sponsor's protocol ID
- H027
- Status last verified
- Mar 2016
- First submitted
- 29 Oct 2014
- Last updated
- 14 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Change in Sleep Architecture and Neuropsychological Performance Following Switch From Atripla to Stribild.
- ClinicalTrials.gov ID
- NCT02283060
- Acronym / sponsor ID
- H027
- Conditions
- HIV
- Keywords
- Atripla, Stribild, HIV, Sleep architecture, Neuropsychological performance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of HawaiiUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Sep 2014
- Primary completion
- Jul 2016 (estimated)
- Study completion
- Aug 2016 (estimated)
- First posted
- 5 Nov 2014 (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.
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.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stribild switch arm | Experimental | Drug: StribildPatient to be taken off Atripla and switched to Stribild (co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) -one tablet taken daily with food |
| Atripla control arm | Active comparator | Drug: AtriplaPatient to continue taking Atripla (co-formulated efavirenz/emtricitabine/ tenofovir disoproxil fumarate) - one tablet taken daily at bedtime on an empty stomach |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (22 listed)
- 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
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 |
|---|---|---|
| StribildAlso: Co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarateTo be administered orally, once daily with food. | Drug | Stribild switch arm |
| AtriplaAlso: Co-formulated efavirenz/emtricitabine/ tenofovir disoproxil fumarateTo be administered orally, once daily at bedtime on an empty stomach | Drug | Atripla control arm |
Primary outcome
Change in sleep architecture assessed by formal sleep study
Time frame: 12 weeks
Change in sleep architecture as assessed by formal sleep study
Change in neuropsychological performance global and subdomain neuropsychological test scores
Time frame: 12 weeks
Change in global and subdomain neuropsychological test scores
3 secondary outcomes
Change in Pittsburgh Sleep Quality Index Score
Time frame: 12 weeks
Change in the frequency of use of sleep medications
Time frame: 12 weeks
Change in the quality of life index score
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2016.
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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.
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 Stribild and Atripla in people with HIV, run by University of Hawaii at 1 site in United States.
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 5 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 14 Mar 2016. 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 United States. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lorna Nagamine, RN (808-692-1333, lornan@hawaii.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in sleep architecture assessed by formal sleep study (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 14 Mar 2016.