A study looking at the effects of switching anti-HIV therapy in people with HIV who have difficulty sleeping
| ISRCTN | ISRCTN17508886 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17508886 |
| EudraCT/CTIS number | 2019-004007-12 |
| IRAS number | 272955 |
| Secondary identifying numbers | CPMS 44049, IRAS 272955 |
- Submission date
- 06/04/2020
- Registration date
- 23/04/2020
- Last edited
- 20/06/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Current plain English summary as of 03/03/2022:
Background and study aims
Current anti-HIV therapy is very effective at controlling the HIV virus and keeping people well. But there is still much that isn’t known about how taking the drugs affect some parts of the body, such as the nervous system. It also isn’t known what effect different drugs might have on things like how well people sleep. Within one family of HIV drugs, called integrase inhibitors, it is thought that difficulty sleeping is higher when taking a drug called dolutegravir. The researchers of this study want to see if taking a different drug from within this family, called bictegravir, might cause less difficulties sleeping.
Who can participate?
HIV-positive people who are generally well but have difficulty sleeping (insomnia), 18 years old and above, who have been taking a drug called dolutegravir plus either one or two NRTIs.
What does the study involve?
Participants will be allocated by chance to either continue taking dolutegravir plus either one or two NRTIs or to switch to taking a drug called Biktarvry, which contains bictegravir. Participants will attend visits over about a 5-month period. There will be eight visits in total. Six visits will be at the routine clinic where blood and urine will be collected and several questionnaires completed. Two visits will be at a separate imaging centre where a brain scan will be performed.
What are the possible benefits and risks of participating?
The information gained from this study may be of benefit in the treatment of people with HIV in the future. There are no direct benefits for participating in this study. Having blood taken is uncomfortable but rarely results in any significant problems. Side effects that have been noted with taking blood include feeling light-headed or faint, fainting, formation of a blood clot, bruising and/or infection at the site of the needlestick. It is possible that if the anti-retroviral drugs in this study are given to a pregnant woman it will harm the foetus. Pregnant women must not therefore take part in this study, neither should women who plan to become pregnant during the study. Women who are at risk of pregnancy will be asked to have pregnancy tests during the study. Women who could become pregnant must use a highly effective contraceptive during this study. This also applies to men with heterosexual partners who could become pregnant. Any participant who finds out that they or their partner has become pregnant while taking part in the study must immediately notify the research doctor. Depending on which group participants are randomly allocated to they may change their anti-HIV therapy at the start and towards the end of the study. This is being done in a way that it is expected that the anti-HIV therapy will continue to work effectively. Indeed, many studies have looked at switching anti-HIV therapy and shown this to be both safe and effective. Within the study, participants will be monitored closely to check that their anti-HIV therapy continues to be effective. However, the researchers cannot guarantee that switching anti-HIV therapy will not pose any risks to participants. Like all medicines, the medicines in this study can cause side effects, although not everybody gets them. The more serious or common side effects with a known or possible relationship to Biktarvy are listed below. The list does not include side effects seen with dolutegravir or NRTIs, as participants will already have been made aware of these when they started this medicine. During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and lifestyle, and in the case of blood lipids sometimes to the HIV medicines themselves. Common side effects (may affect up to 1 in 10 people): depression, abnormal dreams, headache, dizziness, diarrhoea, nausea (feeling sick), fatigue (tiredness). Uncommon side effects (may affect up to 1 in 100 people): suicidal thoughts and attempt (particularly in patients who have had depression or mental health problems before). Rare side effects (may affect up to 1 in 1000 people): Stevens-Johnson syndrome (SJS). Side effects with an unknown frequency (frequency can’t be estimated from the available data): bone problems.
Where is the study run from?
1. St Mary’s Hospital (UK)
2. Royal Sussex County Hospital (UK)
When is the study starting and how long is it expected to run for?
November 2018 to May 2023
Who is funding the study?
Gilead Sciences (USA)
Who is the main contact?
Nicki Doyle
n.doyle@imperial.ac.uk
Previous plain English summary:
Background and study aims
Current anti-HIV therapy is very effective at controlling the HIV virus and keeping people well. But there is still much that isn’t known about how taking the drugs affect some parts of the body, such as the nervous system. It also isn’t known what effect different drugs might have on things like how well people sleep. Within one family of HIV drugs, called integrase inhibitors, it is thought that difficulty sleeping is higher when taking a drug called dolutegravir. The researchers of this study want to see if taking a different drug from within this family, called bictegravir, might cause less difficulties sleeping.
Who can participate?
HIV-positive people who are generally well but have difficulty sleeping (insomnia), 18 years old and above, who have been taking a drug called Triumeq (which contains dolutegravir)
What does the study involve?
Participants will be allocated by chance to either continue taking Triumeq or to switch to taking a drug called Biktarvry, which contains bictegravir. Participants will attend visits over about a 5-month period. There will be eight visits in total. Six visits will be at the routine clinic where blood and urine will be collected and several questionnaires completed. Two visits will be at a separate imaging centre where a brain scan will be performed.
What are the possible benefits and risks of participating?
The information gained from this study may be of benefit in the treatment of people with HIV in the future. There are no direct benefits for participating in this study. Having blood taken is uncomfortable but rarely results in any significant problems. Side effects that have been noted with taking blood include feeling light-headed or faint, fainting, formation of a blood clot, bruising and/or infection at the site of the needlestick. It is possible that if the anti-retroviral drugs in this study are given to a pregnant woman it will harm the foetus. Pregnant women must not therefore take part in this study, neither should women who plan to become pregnant during the study. Women who are at risk of pregnancy will be asked to have pregnancy tests during the study. Women who could become pregnant must use a highly effective contraceptive during this study. This also applies to men with heterosexual partners who could become pregnant. Any participant who finds out that they or their partner has become pregnant while taking part in the study must immediately notify the research doctor. Depending on which group participants are randomly allocated to they may change their anti-HIV therapy at the start and towards the end of the study. This is being done in a way that it is expected that the anti-HIV therapy will continue to work effectively. Indeed, many studies have looked at switching anti-HIV therapy and shown this to be both safe and effective. Within the study, participants will be monitored closely to check that their anti-HIV therapy continues to be effective. However, the researchers cannot guarantee that switching anti-HIV therapy will not pose any risks to participants. Like all medicines, the medicines in this study can cause side effects, although not everybody gets them. The more serious or common side effects with a known or possible relationship to Biktarvy are listed below. The list does not include side effects seen with Triumeq, as participants will already have been made aware of these when they started this medicine. During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and lifestyle, and in the case of blood lipids sometimes to the HIV medicines themselves. Common side effects (may affect up to 1 in 10 people): depression, abnormal dreams, headache, dizziness, diarrhoea, nausea (feeling sick), fatigue (tiredness). Uncommon side effects (may affect up to 1 in 100 people): suicidal behaviour. Side effects with an unknown frequency (frequency can’t be estimated from the available data): bone problems.
Where is the study run from?
1. St Mary’s Hospital (UK)
2. Royal Sussex County Hospital (UK)
When is the study starting and how long is it expected to run for?
November 2018 to May 2022
Who is funding the study?
Gilead Sciences (USA)
Who is the main contact?
Nicki Doyle
n.doyle@imperial.ac.uk
Contact information
Scientific
Ground Floor, BSMS Medical Research Building
University of Sussex
Falmer
Brighton
BN1 9PX
United Kingdom
| Phone | +44 (0)1273 523087 |
|---|---|
| J.Vera@bsms.ac.uk |
Study information
| Study design | Randomized; Both; Design type: Treatment, Drug, Qualitative |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet: Nicki Doyle n.doyle@imperial.ac.uk |
| Scientific title | Brain connectivity and patient-reported outcomes in people with HIV (PWH) with symptoms of insomnia switching integrase inhibitor-based ART: a randomised controlled study |
| Study acronym | BIC CNS |
| Study hypothesis | In people with HIV with symptoms of insomnia, switching from a dolutegravir to bictegravir based antiretroviral therapy regimen will be associated with improvements in brain connectivity measured via functional MRI. |
| Ethics approval(s) | Approved 20/05/2020, South Central - Oxford C Research Ethics Committee (Level 3, Block B, Whitefriars Building, Bristol Research Ethics Committee Centre, BS1 2NT, UK; +44 (0)207 104 8241 / 8041; oxfordc.rec@hra.nhs.uk), REC ref: 20/SC/0116 |
| Condition | Human immunodeficiency virus [HIV] disease |
| Intervention | Current intervention as of 03/03/2022: 46 people with HIV taking a drug called dolutegravir, plus one or two other drugs called NRTIs (nucleoside-reverse-transcriptase-inhibitors) for at least 4 months with an undetectable level of HIV virus will be enrolled. Brain function measures will be assessed via the following methods: i) Brain MR imaging, ii) patient reported outcomes (PRO). At baseline (day 0), all participants will undergo assessment of these brain function measures. Participants will then be randomised on a 1:1 basis (50% chance of each group) to either: 1. Switch anti-retroviral therapy from dolutegravir plus either one or two NRTIs to another drug called Biktarvy™ (which contains drugs bictegravir, emtricitabine & tenofovir alafenamide) 2. Or, remain on dolutegravir plus either one or two NRTIs. Randomisation will be stratified by recruiting site, sex at birth, age at screening, and participant’s handedness and will be done on a 1:1 basis. Biktarvy: 50 mg bictegravir/200 mg emtricitabine/25 mg tenofovir alafenamide - one tablet, orally, once daily. Dolutegravir 50mg (as part of a regimen consisting of dolutegravir plus either one or two nucleoside-reverse-transcriptase-inhibitors [NRTIs]) - one tablet, orally, once daily. Study visits will occur at day 30, day 60, day 120 and day 150. At the day 120 visit, assessment of MRI brain function measures and PRO will be repeated, and participants will resume/remain on their usual pre-study antiretroviral regimen (dolutegravir plus either one or two NRTIs). An end of study visit will be performed at day 150. Participants will attend for 6 clinic visits in total at which they will have a physical examination, have blood collected for safety tests as well as an HIV viral load (the level of HIV virus in the blood) and a CD4 count (a measure of the immune system) at screening & baseline. Any female participants will also have urine collected for a pregnancy test. At the screening and day 120 visit they will complete a short questionnaire relating to their insomnia. At baseline and day 120 they will complete several questionnaires relating to sleep, side effects from anti-HIV medication, food cravings, and quality of life. At baseline and day 120 a research blood sample will be collected and stored for future, ethically approved, research in keeping with the results of this study. In addition, participants will attend two imaging visits at a different location to have brain scans. They will be asked to complete various tasks whilst lying flat within the scanner. Previous interventions as of 17/06/2021: 46 people with HIV taking a drug called Triumeq™ (which contains drugs called dolutegravir, abacavir & lamivudine) for at least 4 months with an undetectable level of HIV virus will be enrolled. Brain function measures will be assessed via the following methods: i) Brain MR imaging, ii) patient reported outcomes (PRO). At baseline (day 0), all participants will undergo assessment of these brain function measures. Participants will then be randomised on a 1:1 basis (50% chance of each group) to A) switch anti-retroviral therapy from Triumeq™ to another drug called Biktarvy™ (which contains drugs bictegravir, emtricitabine & tenofovir alafenamide) or B) remain on Triumeq™. Randomisation will be stratified by recruiting site, sex at birth, age at screening, and participant’s handedness and will be done on a 1:1 basis. Biktarvy: 50 mg bictegravir/200 mg emtricitabine/25 mg tenofovir alafenamide - one tablet, orally, once daily. Triumeq: 50 mg dolutegravir/600 mg abacavir/300 mg lamivudine - one tablet, orally, once daily. Study visits will occur at day 30, day 60, day 120 and day 150. At the day 120 visit, assessment of MRI brain function measures and PRO will be repeated, and participants will resume/remain on their usual pre-study antiretroviral regimen (Triumeq™). An end of study visit will be performed at day 150. Participants will attend for 6 clinic visits in total at which they will have a physical examination, have blood collected for safety tests as well as an HIV viral load (the level of HIV virus in the blood) and a CD4 count (a measure of the immune system) at screening & baseline. Any female participants will also have urine collected for a pregnancy test. At the screening and day 120 visit they will complete a short questionnaire relating to their insomnia. At baseline and day 120 they will complete several questionnaires relating to sleep, side effects from anti-HIV medication, food cravings, and quality of life. At baseline and day 120 a research blood sample will be collected to measure novel biomarkers of inflammation. In addition, participants will attend two imaging visits at a different location to have brain scans. They will be asked to complete various tasks whilst lying flat within the scanner. Previous interventions: 46 people with HIV taking a drug called Triumeq™ (which contains drugs called dolutegravir, abacavir & lamivudine) for at least 4 months with an undetectable level of HIV virus will be enrolled. Brain function measures will be assessed via the following methods: i) Brain MR imaging, ii) patient reported outcomes (PRO). At baseline (day 0), all participants will undergo assessment of these brain function measures. Participants will then be randomised on a 1:1 basis (50% chance of each group) to A) switch anti-retroviral therapy from Triumeq™ to another drug called Biktarvy™ (which contains drugs bictegravir, emtricitabine & tenofovir alafenamide) or B) remain on Triumeq™. Randomisation will not be stratified for any baseline characteristics and will be done on a 1:1 basis. Biktarvy: 50 mg bictegravir/200 mg emtricitabine/25 mg tenofovir alafenamide - one tablet, orally, once daily. Triumeq: 50 mg dolutegravir/600 mg abacavir/300 mg lamivudine - one tablet, orally, once daily. Study visits will occur at day 30, day 60, day 120 and day 150. At the day 120 visit, assessment of MRI brain function measures and PRO will be repeated, and participants will resume/remain on their usual pre-study antiretroviral regimen (Triumeq™). An end of study visit will be performed at day 150. Participants will attend for 6 clinic visits in total at which they will have a physical examination, have blood collected for safety tests as well as an HIV viral load (the level of HIV virus in the blood) and a CD4 count (a measure of the immune system) at screening & baseline. Any female participants will also have urine collected for a pregnancy test. At the screening and day 120 visit they will complete a short questionnaire relating to their insomnia. At baseline and day 120 they will complete several questionnaires relating to sleep, side effects from anti-HIV medication, food cravings, and quality of life. At baseline and day 120 a research blood sample will be collected for storage. In addition, participants will attend two imaging visits at a different location to have brain scans. They will be asked to complete various tasks whilst lying flat within the scanner. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Dolutegravir, abacavir, lamivudine, bictegravir, emtricitabine, tenofovir alafenamide |
| Primary outcome measure | 1. Cerebral function parameters measured using MRI at baseline and day 120 2. Sleep, symptoms associated with antiretroviral therapy and health-related quality of life measured using validated patient-reported outcome questionnaires (HIV symptom index, Short form -36, Pittsburgh sleep quality index, Work productivity and activity impairment questionnaire, Epworth sleepiness scale, Fatigue severity scale of sleep disorders, Food cravings questionnaire – trait & state) measured at baseline and day 120 |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 23/11/2018 |
| Overall study end date | 11/05/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 46; UK Sample Size: 46 |
| Total final enrolment | 19 |
| Participant inclusion criteria | Current participant inclusion criteria as of 16/06/2022: 1. HIV-1 positive 2. Age ≥18 years 3. Plasma HIV RNA <50 copies/ml at screening and on at least one other occasion over the last 12 months 4. Acceptable medical history and laboratory parameters (haematology and chemistry) in the opinion of the investigator 5. On a stable antiretroviral regimen comprising of dolutegravir plus either one or two NRTIs once daily for >4 months 6. A total score of ≥8 on the Insomnia Severity Index 7. BMI ≥18 Previous participant inclusion criteria as of 03/03/2022: 1. HIV-1 positive 2. Age ≥18 years 3. Plasma HIV RNA <50 copies/ml at screening and on at least one other occasion over the last 12 months 4. Acceptable medical history and laboratory parameters (haematology and chemistry) in the opinion of the investigator 5. On a stable antiretroviral regimen comprising of dolutegravir plus either one or two NRTIs once daily for >4 months 6. A total score of ≥8 on the Insomnia Severity Index 7. BMI of 18-32, inclusive Previous participant inclusion criteria as of 17/06/2021: 1. HIV-1 positive 2. Age ≥18 years 3. Plasma HIV RNA <50 copies/ml at screening and on at least one other occasion over the last 12 months 4. Acceptable medical history and laboratory parameters (haematology and chemistry) in the opinion of the investigator 5. On a stable antiretroviral regimen comprising of Triumeq™ once daily for >4 months 6. A total score of ≥8 on the Insomnia Severity Index 7. BMI of 18-32, inclusive Previous participant inclusion criteria: 1. HIV-1 positive 2. Age > = 18 years 3. Plasma HIV RNA < 50 copies/mL at screening and on at least one other occasion over the last 3 months 4. Acceptable medical history and laboratory parameters (haematology and chemistry) in the opinion of the investigator 5. On a stable antiretroviral regimen comprising of Triumeq™ once daily for > 4 months 6. A total score of 8 or greater in the Insomnia Severity Index 7. BMI 18 - 32, inclusive |
| Participant exclusion criteria | 1. Significant neurological disease 2. Current history of major depression or psychosis 3. Diagnosed sleep disorder (sleep apnoea, narcolepsy) 4. Current medication which is likely to interfere with sleep 5. Recent head injury (past 30 days) 6. Current alcohol abuse or drug of abuse dependence 7. Active opportunistic infection or significant co-morbidities 8. Pregnancy |
| Recruitment start date | 05/10/2021 |
| Recruitment end date | 31/01/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Eastern Road
Brighton
BN2 5BE
United Kingdom
Praed Street
London
W2 1NY
United Kingdom
Sponsor information
University/education
c/o Dr Antony Walsh
Research and Enterprise Services
Falmer House
Brighton
BN1 9QF
England
United Kingdom
| Phone | +44 (0)1273 872748 |
|---|---|
| researchsponsorship@sussex.ac.uk | |
| Website | http://www.sussex.ac.uk/ |
"ROR" |
https://ror.org/00ayhx656 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Gilead, Gilead Sciences, Inc.
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/03/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal and presentation at relevant medical conferences within a year of the overall trial end date. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 26/07/2023 | No | No |
Editorial Notes
20/06/2023: The following changes were made to the study record:
1. The overall trial end date was changed from 30/06/2023 to 11/05/2023.
2. The intention to publish date was changed from 19/09/2023 to 01/03/2024.
05/10/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 17/08/2022 to 31/01/2023.
2. The overall trial end date was changed from 17/02/2023 to 30/06/2023.
16/06/2022: The participant inclusion criteria have been updated.
17/05/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 05/05/2022 to 17/08/2022.
2. The overall end date was changed from 05/10/2022 to 17/02/2023.
3. The intention to publish date was changed from 30/04/2023 to 19/09/2023.
4. The plain English summary was updated to reflect these changes.
03/03/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/07/2021 to 05/10/2021.
2. The recruitment end date has been changed from 31/12/2021 to 05/05/2022.
3. The overall trial end date has been changed from 31/05/2022 to 05/10/2022.
4. The intention to publish date has been changed from 30/11/2022 to 30/04/2023.
5. The intervention has been updated.
6. The participant inclusion criteria have been updated.
7. The plain English summary has been updated.
17/06/2021: The following changes have been made:
1. The recruitment start date has been changed from 01/11/2020 to 01/07/2021.
2. The recruitment end date has been changed from 30/04/2021 to 31/12/2021.
3. The overall trial end date has been changed from 30/09/2021 to 31/05/2022 and the plain English summary has been updated to reflect this change.
4. The intention to publish date has been changed from 30/09/2022 to 30/11/2022.
5. The ethics approval date has been added.
6. The interventions have been updated.
7. The trial phase has been changed from "Not Applicable" to "Phase IV".
8. The participant inclusion criteria have been updated.
9. A trial participating centre name has been changed from "Brighton and Sussex University Hospitals NHS Trust" to "University Hospitals Sussex NHS Foundation Trust".
06/04/2020: Trial's existence confirmed by the NIHR.
