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Trial record 2 of 82 for:    Elvitegravir OR Elvitegravir[TREATMENT] AND HIV [CONDITION]

Advanced Neuroimaging Evaluation of the Central Nervous System Biological Changes Associated With Efavirenz Therapy and Switch to an Elvitegravir-based Regimen

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ClinicalTrials.gov Identifier: NCT01929759
Recruitment Status : Completed
First Posted : August 28, 2013
Results First Posted : July 28, 2017
Last Update Posted : July 28, 2017
Sponsor:
Collaborators:
Brigham and Women's Hospital
Gilead Sciences
Information provided by (Responsible Party):
Nina Lin, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition HIV Disease
Intervention Drug: Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)
Enrollment 10
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Drug Switching
Hide Arm/Group Description

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Period Title: Overall Study
Started 10
Completed 10
Not Completed 0
Arm/Group Title Drug Switching
Hide Arm/Group Description

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
<=18 years 0
Between 18 and 65 years 10
>=65 years 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
1
  10.0%
Male
9
  90.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants
10
Baseline measures for Neurometabolites Based on MRS   [1] 
Mean (Standard Deviation)
Unit of measure:  Arbitrary units
Number Analyzed 10 participants
Posterior cingulate creatine 19.09  (2.27)
Posterior cingulate glutamate 25.36  (3.73)
Posterior cingulate GABA 4.99  (1.29)
Anterior cingulate creatine 14.06  (2.44)
Anterior cingulate glutamate 19.16  (3.11)
Anterior cingulate GABA 4.21  (1.18)
[1]
Measure Description: The arbitrary units are expressed as the output from MRS software. While similar to concentration (mM) due to assumptions in the software, it is best expressed as arbitrary units for comparison from baseline to the second time point.
1.Primary Outcome
Title Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS)
Hide Description Assess the change in levels of neuro-metabolites measured by MRS from week 0 (before switching to the efavirenz-based therapy) and then at week 8 (after completing 9 weeks of integrase-inhibitor based regimen with Stribild). Two areas of the brain: 1) posterior cingulate gyrus and 2) anterior cingulate will be assessed for the levels of brain Cr, GABA and GLU.
Time Frame week 0 to week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The arbitrary units are expressed as the output from MRS software. While similar to concentration (mM) due to assumptions in the software, it is best expressed as arbitrary units for comparison from week 0 to week 8.
Arm/Group Title Drug Switching
Hide Arm/Group Description:

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: arbitrary units
Posterior Cingulate Creatine 19.61  (3.44)
Posterior Cingulate Glutamate 24.54  (3.69)
Posterior Cingulate GABA 6.71  (1.07)
Anterior Cingulate Creatine 12.08  (4.63)
Anterior Cingulate Glutamate 16.16  (6.00)
Anterior Cingulate GABA 3.67  (1.52)
2.Primary Outcome
Title Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI)
Hide Description Assess changes in neural activation correlated with affective disturbances associated with efavirenz-based therapy using fMRI employing an Emotional Word/Go-NoGo task paradigm that probes affective symptomatologies typical with EFV use, specifically anxiety/dysphoria and affective dysregulation and their association with changes in cognitive function. Four brain regions of interests (ROIs) are specified to show the differential frontal-limbic activation patterns in the task-evoked neural responses to the 3 linear contrasts of Pre-switch / Post-switch / Pre- vs. Post-switch: [Negative Word vs. Neutral Word] x [No-Go Trial Block vs. Go Trial Block]: anterior Frontal Pole (aFP), posterior Cingulate Gyrus (pCG), dorsal anterior Cingulate Gyrus (daCG), Left Hippocampus (LHC). A linear mixed-effects model is utilized to examine the effect sizes of the key Regimen/Condition contrasts, with the Subject factor as the random-effect and Age incorporated as a co-variate of no interest.
Time Frame week 0 and week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
8 of 10 enrolled patients passed QA testing to be included in the final analyses. The 3 linear contrasts of Pre-switch/Post-switch/Pre- vs. Post-switch: [Neg vs.Neu] x [No-Go vs. Go] are reported as z-score (standardized effect size measures with SD=1). Z-score is obtained for each subject, group Z-score is obtained via a mixed-effects model.
Arm/Group Title Drug Switching
Hide Arm/Group Description:

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: z-score
PreVsPostXNegVsNeuXNoGoVsGo: aFP 3.42
PreVsPostXNegVsNeuXNoGoVsGo: pCG 3.90
PreVsPostXNegVsNeuXNoGoVsGo: daCG -2.76
PreVsPostXNegVsNeuXNoGoVsGo:LHC -2.96
Pre: NegVsNeuXNoGoVsGo: aFP 3.39
Pre: NegVsNeuXNoGoVsGo:pCG 3.61
Pre: NegVsNeuXNoGoVsGo: daCG -3.15
Pre: NegVsNeuXNoGoVsGo: LHC -2.27
Post: NegVsNeuXNoGoVsGo: aFP -3.17
Post: NegVsNeuXNoGoVsGo: pCG -2.66
Post: NegVsNeuXNoGoVsGo: daCG 3.69
Post: NegVsNeuXNoGoVsGo: LHC 3.47
3.Secondary Outcome
Title Change in Other Neurometabolite Measured by MRS Between Week 0 and Week 8
Hide Description Use MRS to evaluate a fuller panel of known neurometabolites (in addition to the primary endpoints) between week 0 and week 8 to identify prominent and significant changes associated with EFV use.
Time Frame week 0 to week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The arbitrary units are expressed as the output from MRS software. While similar to concentration (mM) due to assumptions in the software, it is best expressed as arbitrary units for comparison from week 0 to week 8.
Arm/Group Title Drug Switching
Hide Arm/Group Description:

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: arbitrary units
Posterior cingulate glutathione 5.06  (1.17)
Posterior cingulate aspartate 3.69  (0.98)
Anterior cingulate glutathione 3.17  (1.34)
Anterior cingulate aspartate 2.57  (1.29)
4.Secondary Outcome
Title Neurocognitive Changes
Hide Description

Assess for changes in cognitive and affective function prior to and after switching off EFV-based regimen. Indexes used to access neurocognitive changes included:

  1. Wechsler Adult Intelligence Scale (WAIS-R) Digital Symbol Substitution Test: sensitive to brain damage, dementia, age and depressive changes. Range of 0-100, the higher the score the better the person's performance
  2. Hamilton Rating Scale for Depression (HAMD): Measure of depression. Score of 0-7 is normal, score of >20 is moderate/severe depression
  3. Depression Anxiety Stress Scale (DASS-21) the lower the score, the less severe depression, anxiety and stress. Scale range of 0-63
  4. Frontal Systems Behavior Scale (FRSBE): Increased score indicates greater behavioral impairment associated with frontal systems, range 37.2 to 186

6. Spielberger state trait anxiety inventory (STAI): the higher the score the greater then anxiety level, range of 20 to 80.

Time Frame week 0 and week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Several Indexes were used to access neurocognitive changes: WAIS, HAMD, FRSBE, DASS-21, STAI.

Participants were given these tests prior to and after drug switch.

Arm/Group Title Drug Switching
Hide Arm/Group Description:

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
pre-switch WAIS 49.3  (11.62)
post-switch WAIS 53.4  (12.60)
pre-switch FRSBE 77.5  (10.01)
post-switch FRSBE 70.4  (13.00)
pre-switch HAMD 5.5  (3.41)
post-switch HAMD 2.8  (2.20)
pre-switch DASS depression 7.6  (8.58)
post-switch DASS depression 3.4  (4.72)
pre-swtich STAI 28.8  (5.87)
post-switch STAI 24.2  (3.19)
5.Secondary Outcome
Title Fasting Lipid Profile
Hide Description Measure the change in fasting lipid panel prior to and after switching off EFV-based regimen.
Time Frame 8 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Change in fasting lipid profile was measured: total cholesterol, HDL and LDL levels.
Arm/Group Title Drug Switching
Hide Arm/Group Description:

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mg/dl
pre-switch Total cholesterol 178.8  (24.24)
post-switch Total cholesterol 168.5  (20.84)
pre-switch HDL 52.6  (16.49)
post-switch HDL 52.3  (19.42)
pre-switch LDL 106.1  (22.96)
post-switch LDL 97.4  (19.36)
pre-switch triglyceride 101.3  (50.39)
post-switch triglyceride 94.5  (30.50)
6.Secondary Outcome
Title Sleep Quality
Hide Description Assess for changes in sleep pattern and quality prior to and after switching off EFV-based regimen through a self-administered Pittsburg Sleep Quality Index (PSQI). Measure consists of 19 items with each weighted on 0-3 scale and the sum produces a total score, which ranges from 0-21. The lower the score the healthier the sleep quality; minimum Score = 0 (better); maximum Score = 21 (worse).
Time Frame week 0 and week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Drug Switching
Hide Arm/Group Description:

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
pre-switch PSQI index 4.8  (2.30)
post-switch PSQI index 3.1  (1.66)
7.Secondary Outcome
Title ART Regimen Preference
Hide Description Evaluate patient preference in ART regimen (Atripla, EFV/FTC/TDF versus EVG/COBI/FTC/TDF) through a self-administered questionnaire.
Time Frame week 0 and week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients were surveyed at the end of the study with a single question regarding their ART preference. They are asked to pick one of the 3 answers: 1. prefer Atripla, 2. prefer the new drug (Stribild) or 3. no preference. The number of patients who would like to switch to study drug, Stribild, are indicated by the percentage.
Arm/Group Title Drug Switching
Hide Arm/Group Description:

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
Prefers Stribld
9
  90.0%
Prefers Atripla
0
   0.0%
No preference
1
  10.0%
8.Secondary Outcome
Title Markers of Immune Activation
Hide Description Change in markers of immune activation and inflammation associated with change to Stibild: sCD14, IP-10,sCD163, IL-6)
Time Frame week 0 and week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Inflammatory markers were measured pre- and post-drug switch from Atripla to Stibild.
Arm/Group Title Drug Switching
Hide Arm/Group Description:

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: pg/ML
pre-switch sCD14 3329000  (566684)
post-switch sCD14 2879000  (867793)
pre-switch IP-10 237.3  (204.8)
post-switch IP-10 224.2  (201)
pre-switch sCD163 732000  (559000)
post-switch sCD163 599500  (319200)
pre-switch MCP-1 102.2  (68)
post-switch MCP-1 91.39  (43.02)
pre-switch IL-6 1.255  (0.5921)
post-switch IL-6 1.301  (0.7115)
pre-switch TNFR1 833.2  (222.1)
post-switch TNFR1 878.1  (198.8)
9.Secondary Outcome
Title Effect of EFV and Its Metabolites
Hide Description Level of EFV (efavirenz) in Atripla and its two known metabolites known to cause cerebral side effects, 7-hydroxy (OH) EFV and 8-OH EFV, were measured in the plasma prior to switch off Atripla and after 8 weeks of RAL-based regimen (no EFV).
Time Frame week 0 and week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Drug Switching
Hide Arm/Group Description:

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: participants
Number with detectable 7-OH and 8-OH (pre-switch) 10
Number with detectable 7-OH and 8-OH (post-switch) 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Drug Switching
Hide Arm/Group Description

Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.

Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks

All-Cause Mortality
Drug Switching
Affected / at Risk (%)
Total   0/10 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Drug Switching
Affected / at Risk (%)
Total   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Drug Switching
Affected / at Risk (%)
Total   0/10 (0.00%) 
One participant did not have repeat fMRI because the pre-switch fMRI was not done correctly. The patient did not fully understand the tasks to be performed, therefore no repeat follow up fMRI was done without the comparator study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Nina Lin
Organization: Boston Medical Center, Boston University School of Medicine
Phone: 617-414-5242
Responsible Party: Nina Lin, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01929759     History of Changes
Other Study ID Numbers: NeuroHIV001
First Submitted: August 23, 2013
First Posted: August 28, 2013
Results First Submitted: March 27, 2017
Results First Posted: July 28, 2017
Last Update Posted: July 28, 2017