HIV Disease
Conditions
Keywords
HIV, neurocognitive symptoms, efavirenz, elvitegravir, neurometabolites
Brief summary
In this study we will use a multi-modal imaging approach of MRS and fMRI to comprehensively assess the biological changes in the brain associated with EFV-based regimen (EFV/FTC/TDF), specifically alterations in the brain circuitry, function and local neurochemistry, and their correlation with neuropsychological function. In a cohort of HIV-infected patients who are clinically stable on the commonly use regimen of EFV/emtricitabine (FTC)/truvada (TDF) or Atripla, we propose to replace the EFV component with a new integrase inhibitor, elvitegravir (EVG) boosted with cobicistat (COBI), given as the EVG/COBI/FTC/TDF Single Tablet Regimen (STR) to evaluate the EFV-related neural alterations. This is a multidisciplinary study which involves a team of infectious disease experts in the field of HIV, neuroradiologists with expertise in fMRI and MRS techniques to study various central nervous system and psychiatric disorders and a psychiatrist with experience and expertise in research on abnormalities of affective and motivational processing in the context of neuropsychiatric disorders. We will utilize the established clinical research platform in the Infectious Disease outpatient clinical practice at the Brigham and Women's Hospital, where there is currently have many ongoing HIV-related studies and a large panel of HIV-infected patients motivated to be involved in clinically relevant research. We propose to use advanced neuroimaging to measure biologically changes in the brain associated with long-term EFV use with the following specific aims: 1. Determine changes in neurometabolites measured by MRS in the brain associated with long-term EFV use 2. Assess for alterations in neural activity correlated with affective symptoms associated with EFV vs STR use using fMRI, and their associations with changes in neurometabolites assessed by MRS, and with changes in cognition assessed by Trail Making and Digit Substitution Tests. 3. Determine changes in emotion, cognition and sleep quality after switching from EFV to STR, and how they correlate with subject treatment preference. This clinical study will extend our current understanding of EFV neurotoxicity by further defining the nature of these biological changes. Further elucidation of the neurobiological underpinnings of EFV-induced CNS toxicity will have clinical relevance in improving the quality of life and drug adherence of HIV-infected patients on ART, especially among older patients or those with baseline neuropsychiatric disorders, whom at baseline are more vulnerable to neurocognitive decline from long-term HIV infection.
Interventions
DRUGStribild (elvitegravir, cobicistat, emtricitabine and tenofovir)
Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks
Sponsors
Brigham and Women's Hospital
Gilead Sciences
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Treatment switch study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Chronic HIV-infected individuals on suppressive regimen with EFV/FTC/TDF, for at least 6 months * Undetectable HIV-1 RNA virus load for at least 6 months * No co-infections with active hepatitis B and C * Presence of at least moderate symptoms on 2 out of 3 subcores on the DASS * No known active HIV-related and non-HIV related CNS infections * Estimated glomerular filtration rate (EGFR) \>60 ml/min * Consent to switching to EVG/COBI/FTC/TDF * Ages 18 - 65
Exclusion criteria
* History of CNS opportunistic infections or active CNS infections * History of severe psychiatric disorder (excluding depression and anxiety) * History of chronic neurological disorders, such as epilepsy or multiple sclerosis * History of or current significant substance abuse or dependence and/or heavy alcohol use (\>12 oz/wk) * Any women who may be pregnant (positive urine pregnancy test or unprotected sex in 2 weeks prior to scan) or known to be pregnant * Contraindications to undergoing fMRI, including metallic implants, claustrophobia, and medical conditions or medications that significantly affect cerebral blood flow or function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | week 0 to week 8 | 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. |
| Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | week 0 and week 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Lipid Profile | 8 weeks | Measure the change in fasting lipid panel prior to and after switching off EFV-based regimen. |
| Sleep Quality | week 0 and week 8 | 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). |
| Change in Other Neurometabolite Measured by MRS Between Week 0 and Week 8 | week 0 to week 8 | 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. |
| Markers of Immune Activation | week 0 and week 8 | Change in markers of immune activation and inflammation associated with change to Stibild: sCD14, IP-10,sCD163, IL-6) |
| Effect of EFV and Its Metabolites | week 0 and week 8 | 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). |
| ART Regimen Preference | week 0 and week 8 | Evaluate patient preference in ART regimen (Atripla, EFV/FTC/TDF versus EVG/COBI/FTC/TDF) through a self-administered questionnaire. |
| Neurocognitive Changes | week 0 and week 8 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Drug Switching 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 | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Drug Switching |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Baseline measures for Neurometabolites Based on MRS Anterior cingulate creatine | 14.06 arbitrary units STANDARD_DEVIATION 2.44 |
| Baseline measures for Neurometabolites Based on MRS Anterior cingulate GABA | 4.21 arbitrary units STANDARD_DEVIATION 1.18 |
| Baseline measures for Neurometabolites Based on MRS Anterior cingulate glutamate | 19.16 arbitrary units STANDARD_DEVIATION 3.11 |
| Baseline measures for Neurometabolites Based on MRS Posterior cingulate creatine | 19.09 arbitrary units STANDARD_DEVIATION 2.27 |
| Baseline measures for Neurometabolites Based on MRS Posterior cingulate GABA | 4.99 arbitrary units STANDARD_DEVIATION 1.29 |
| Baseline measures for Neurometabolites Based on MRS Posterior cingulate glutamate | 25.36 arbitrary units STANDARD_DEVIATION 3.73 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Drug Switching | Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Anterior Cingulate GABA | 3.67 arbitrary units | Standard Deviation 1.52 |
| Drug Switching | Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Posterior Cingulate Creatine | 19.61 arbitrary units | Standard Deviation 3.44 |
| Drug Switching | Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Posterior Cingulate Glutamate | 24.54 arbitrary units | Standard Deviation 3.69 |
| Drug Switching | Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Posterior Cingulate GABA | 6.71 arbitrary units | Standard Deviation 1.07 |
| Drug Switching | Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Anterior Cingulate Creatine | 12.08 arbitrary units | Standard Deviation 4.63 |
| Drug Switching | Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Anterior Cingulate Glutamate | 16.16 arbitrary units | Standard Deviation 6 |
Primary
Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | PreVsPostXNegVsNeuXNoGoVsGo: aFP | 3.42 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | PreVsPostXNegVsNeuXNoGoVsGo: pCG | 3.90 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | PreVsPostXNegVsNeuXNoGoVsGo: daCG | -2.76 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | PreVsPostXNegVsNeuXNoGoVsGo:LHC | -2.96 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Pre: NegVsNeuXNoGoVsGo: aFP | 3.39 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Pre: NegVsNeuXNoGoVsGo:pCG | 3.61 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Pre: NegVsNeuXNoGoVsGo: daCG | -3.15 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Pre: NegVsNeuXNoGoVsGo: LHC | -2.27 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Post: NegVsNeuXNoGoVsGo: aFP | -3.17 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Post: NegVsNeuXNoGoVsGo: pCG | -2.66 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Post: NegVsNeuXNoGoVsGo: daCG | 3.69 z-score |
| Drug Switching | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Post: NegVsNeuXNoGoVsGo: LHC | 3.47 z-score |
Secondary
ART Regimen Preference
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
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug Switching | ART Regimen Preference | Prefers Stribld | 9 Participants |
| Drug Switching | ART Regimen Preference | Prefers Atripla | 0 Participants |
| Drug Switching | ART Regimen Preference | No preference | 1 Participants |
Secondary
Change in Other Neurometabolite Measured by MRS Between Week 0 and Week 8
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Drug Switching | Change in Other Neurometabolite Measured by MRS Between Week 0 and Week 8 | Anterior cingulate aspartate | 2.57 arbitrary units | Standard Deviation 1.29 |
| Drug Switching | Change in Other Neurometabolite Measured by MRS Between Week 0 and Week 8 | Posterior cingulate glutathione | 5.06 arbitrary units | Standard Deviation 1.17 |
| Drug Switching | Change in Other Neurometabolite Measured by MRS Between Week 0 and Week 8 | Posterior cingulate aspartate | 3.69 arbitrary units | Standard Deviation 0.98 |
| Drug Switching | Change in Other Neurometabolite Measured by MRS Between Week 0 and Week 8 | Anterior cingulate glutathione | 3.17 arbitrary units | Standard Deviation 1.34 |
Secondary
Effect of EFV and Its Metabolites
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Drug Switching | Effect of EFV and Its Metabolites | Number with detectable 7-OH and 8-OH (pre-switch) | 10 participants |
| Drug Switching | Effect of EFV and Its Metabolites | Number with detectable 7-OH and 8-OH (post-switch) | 0 participants |
Secondary
Fasting Lipid Profile
Measure the change in fasting lipid panel prior to and after switching off EFV-based regimen.
Time frame: 8 weeks
Population: Change in fasting lipid profile was measured: total cholesterol, HDL and LDL levels.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Drug Switching | Fasting Lipid Profile | pre-switch Total cholesterol | 178.8 mg/dl | Standard Deviation 24.24 |
| Drug Switching | Fasting Lipid Profile | post-switch Total cholesterol | 168.5 mg/dl | Standard Deviation 20.84 |
| Drug Switching | Fasting Lipid Profile | pre-switch HDL | 52.6 mg/dl | Standard Deviation 16.49 |
| Drug Switching | Fasting Lipid Profile | post-switch HDL | 52.3 mg/dl | Standard Deviation 19.42 |
| Drug Switching | Fasting Lipid Profile | pre-switch LDL | 106.1 mg/dl | Standard Deviation 22.96 |
| Drug Switching | Fasting Lipid Profile | post-switch LDL | 97.4 mg/dl | Standard Deviation 19.36 |
| Drug Switching | Fasting Lipid Profile | pre-switch triglyceride | 101.3 mg/dl | Standard Deviation 50.39 |
| Drug Switching | Fasting Lipid Profile | post-switch triglyceride | 94.5 mg/dl | Standard Deviation 30.5 |
Secondary
Markers of Immune Activation
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
Population: Inflammatory markers were measured pre- and post-drug switch from Atripla to Stibild.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Drug Switching | Markers of Immune Activation | pre-switch sCD14 | 3329000 pg/ML | Standard Deviation 566684 |
| Drug Switching | Markers of Immune Activation | post-switch sCD14 | 2879000 pg/ML | Standard Deviation 867793 |
| Drug Switching | Markers of Immune Activation | pre-switch IP-10 | 237.3 pg/ML | Standard Deviation 204.8 |
| Drug Switching | Markers of Immune Activation | post-switch IP-10 | 224.2 pg/ML | Standard Deviation 201 |
| Drug Switching | Markers of Immune Activation | pre-switch sCD163 | 732000 pg/ML | Standard Deviation 559000 |
| Drug Switching | Markers of Immune Activation | post-switch sCD163 | 599500 pg/ML | Standard Deviation 319200 |
| Drug Switching | Markers of Immune Activation | pre-switch MCP-1 | 102.2 pg/ML | Standard Deviation 68 |
| Drug Switching | Markers of Immune Activation | post-switch MCP-1 | 91.39 pg/ML | Standard Deviation 43.02 |
| Drug Switching | Markers of Immune Activation | pre-switch IL-6 | 1.255 pg/ML | Standard Deviation 0.5921 |
| Drug Switching | Markers of Immune Activation | post-switch IL-6 | 1.301 pg/ML | Standard Deviation 0.7115 |
| Drug Switching | Markers of Immune Activation | pre-switch TNFR1 | 833.2 pg/ML | Standard Deviation 222.1 |
| Drug Switching | Markers of Immune Activation | post-switch TNFR1 | 878.1 pg/ML | Standard Deviation 198.8 |
Secondary
Neurocognitive Changes
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Drug Switching | Neurocognitive Changes | pre-switch WAIS | 49.3 units on a scale | Standard Deviation 11.62 |
| Drug Switching | Neurocognitive Changes | post-switch WAIS | 53.4 units on a scale | Standard Deviation 12.6 |
| Drug Switching | Neurocognitive Changes | pre-switch FRSBE | 77.5 units on a scale | Standard Deviation 10.01 |
| Drug Switching | Neurocognitive Changes | post-switch FRSBE | 70.4 units on a scale | Standard Deviation 13 |
| Drug Switching | Neurocognitive Changes | pre-switch HAMD | 5.5 units on a scale | Standard Deviation 3.41 |
| Drug Switching | Neurocognitive Changes | post-switch HAMD | 2.8 units on a scale | Standard Deviation 2.2 |
| Drug Switching | Neurocognitive Changes | pre-switch DASS depression | 7.6 units on a scale | Standard Deviation 8.58 |
| Drug Switching | Neurocognitive Changes | post-switch DASS depression | 3.4 units on a scale | Standard Deviation 4.72 |
| Drug Switching | Neurocognitive Changes | pre-swtich STAI | 28.8 units on a scale | Standard Deviation 5.87 |
| Drug Switching | Neurocognitive Changes | post-switch STAI | 24.2 units on a scale | Standard Deviation 3.19 |
Secondary
Sleep Quality
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Drug Switching | Sleep Quality | pre-switch PSQI index | 4.8 units on a scale | Standard Deviation 2.3 |
| Drug Switching | Sleep Quality | post-switch PSQI index | 3.1 units on a scale | Standard Deviation 1.66 |