The TILT Study: A pilot trial of antiretroviral Therapy Interruption with and without use of interLeukin-Two
| ISRCTN | ISRCTN85996946 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN85996946 |
| Secondary identifying numbers | G0000198 |
- Submission date
- 18/10/2000
- Registration date
- 18/10/2000
- Last edited
- 30/07/2009
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr M Youle
Scientific
Scientific
Department of Thoracic Medicine
Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | |
| Study acronym | TILT |
| Study objectives | Primary: To gain experience in antiretroviral therapy interruptions in patients with viral suppression and increased CD4 count, with and without use of Interleukin-2 (IL-2). In particular, to test the ability to maintain the CD4 count at a level above 150/mm3 during interruption, to evaluate the length of time off therapy that can be safely achieved and to evaluate the ability to "re-suppress" viral load if and when antiretroviral therapy is restarted. This information will be used to guide the design of a larger trial. Secondary: To obtain preliminary data comparing the three strategies with regard to: 1. CD4 count decline to less than 150/mm to the power of three or new Acquired Immume Deficiency Symdrome (AIDS) disease or death 2. Virological failure of therapy (viral load greater than 1000 after having been on antiretroviral therapy for over 16 weeks) by two years 3. Changes in levels of lactates, lipids and bicarbonates 4. Quality of life using the Medical Outcomes Study health status questionnaire for HIV (MOS-HIV) |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Human Immunodeficiency Virus (HIV), Acquired Immune Deficiency Syndrome (AIDS) |
| Intervention | An open, randomised, three arm, controlled trial to study interruption of antiretroviral therapy with or without IL-2 therapy, in individuals with HIV-1 infection and nadir CD4 cell counts greater than 100 x 10^6/1, current CD4 count greater than 300 x 10^6/1 and currently receiving antiretrovirals and with a viral load less than 50 copies/ml for greater than three months. Participants will be randomly allocated 1:1:1 ratio to either: 1. Continue with antiretroviral therapy. If drugs need to be switched for any reason, this should be done without a complete interruption, or 2. Interrupt antiretroviral therapy. Restart with the same regimen when the clinician and patient feel this is warranted. Treatment should certainly be restarted before the CD4 count falls below 200/mm^3. Further treatment interruptions should be considered when viral load is less than 50 for 12 weeks or more and if CD4 count is more than or equal to 300/mm^3, or 3. Give two cycles of IL-2, eight weeks apart, while still on antiretroviral therapy. Then interrupt antiretroviral therapy. Use new cycles of IL-2 and/or reintroduction of antiretroviral therapy if the clinician and patient feel that this is warranted. New cycles of IL-2 and/or antiretroviral therapy should certainly be given before the CD4 count falls below 200/mm^3. Last patient will complete follow up in July 2006. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | interLeukin-Two |
| Primary outcome measure | 1. CD4 decline to les than 100 or new AIDS disease after death 2. Virological failure of therapy at two years after baseline 3. Virological failure of therapy at any time during the two year period after randomisation 4. Changes in levels of total cholesterol 5. Changes in severity of lipodystrophy/ quality of life 6. Incidence of grade three or four adverse |
| Secondary outcome measures | Not provided at time of registration |
| Overall study start date | 20/02/2001 |
| Completion date | 31/08/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 90 - Closed to recruitment - in follow-up |
| Key inclusion criteria | 1. HIV seropositive 2. Adult (18 years or older) HIV-infected therapy naïve patients 3. On Highly Active Anti-retroviral Therapy (HAART) (more than or equal to three ARTs of any of the three main classes) with viral load less than 50 copies/mL for 12 weeks or more 4. CD4 count nadir more than 50/mm^3 5. CD4 lymphocyte count more than or equal to 300/mm^3 6. Signed informed consent obtained |
| Key exclusion criteria | 1. Patients on hydroxyurea or interferons or any immunomodulating agent besides IL-2 2. Age less than 16 3. Prior IL-2 therapy 4. Use of any approved or experimental antiretroviral drug within four months prior to study therapy 5. Concurrent malignancy other than mucocutaneos Kaposi sarcoma or malignancy treated within the past five years 6. Any concurrent or history of AIDS defining illness 7. Use of systemic corticosteroids, chemotherapy or experimental cytotoxic drugs within four weeks prior to study therapy 8. Use of any agent approved or experimental with clinically significant immunomodulatory effects 9. Any Central Nervous System (CNS) abnormality that requires treatment with anti-seizure medication 10. Patients with current or historical Crohn's disease, psoriasis or other autoimmune/inflammatory diseases with potential life threatening complications 11. Pregnant or lactating women 12. Use of recreational drugs/alcohol that in the opinion of the investigator would affect patient safety and/or compliance 13. Patients with any serious psychiatric, medical and/or cognitive disturbance or illness that in the opinion of the investigator may affect safety, compliance or ability to provide written informed consent |
| Date of first enrolment | 20/02/2001 |
| Date of final enrolment | 31/08/2006 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Department of Thoracic Medicine
London
NW3 2QG
United Kingdom
NW3 2QG
United Kingdom
Sponsor information
Medical Research Council (MRC) (UK)
Research council
Research council
20 Park Crescent
London
W1B 1AL
United Kingdom
| Phone | +44 (0)20 7636 5422 |
|---|---|
| clinical.trial@headoffice.mrc.ac.uk | |
| Website | http://www.mrc.ac.uk |
Funders
Funder type
Research council
Medical Research Council (MRC) (UK)
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 30/03/2008 | Yes | No |
