TuberculosisNCT05329415
Tuberculosis Drug Levels and Continuous Glucose Monitoring in Diabetic Patients
An observational study of Tuberculosis and Diabetes Mellitus, run by London North West Healthcare NHS Trust at 1 site in United Kingdom.
Trial summary
Diabetes significantly increases the risk of developing active tuberculosis (TB). Diabetic patients who do develop TB have worse treatment outcomes and overall mortality. TB also worsens blood glucose control in diabetics, the mechanism of which is not well understood. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Diabetes Mellitus
- What is being tested?
- TB Drug Levels
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Feb 2022to May 2024
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants will be recruited from TB clinics at London North West University NHS Trust.
Who may be able to join
- Cases:
- Subject aged 18 years of age or over
- Written, informed consent obtained.
- New diagnosis of tuberculosis and starting on anti-tuberculosis treatment
- Known diagnosis of diabetes or a raised IFCC HbA1c level (>= 48 mmol/mol) at the time of TB diagnosis
- Controls:
Show all 10Show fewer
- Subject aged 18 years of age or over
- Written, informed consent obtained.
- New diagnosis of tuberculosis and starting on anti-tuberculosis treatment
- IFCC HbA1c level < 48mmol/mol and no known diagnosis of diabetes
Who cannot join
- Subject aged under 18 years
- Inability to give informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
London North West University NHS University Trust
London, HA1 3UJ
About this study
Diabetes significantly increases the risk of developing active tuberculosis (TB). Diabetic patients who do develop TB have worse treatment outcomes and overall mortality. TB also worsens blood glucose control in diabetics, the mechanism of which is not well understood. The incidence of type 2 diabetes is rising globally, and consequently diabetes and TB co-infection is increasingly common, and improving outcomes in this cohort is of growing importance.
Low TB drug levels in diabetic patients have been postulated as a reason for these worse outcomes. There is however contradictory evidence in the literature that TB drug levels really are consistently and significantly lower in diabetics compared with non-diabetics. If this were shown to be the case, performing therapeutic drug monitoring in diabetic patients may be a straightforward way to improve outcomes. Improving blood glucose control may also lead to improved outcomes, however there is nothing previously in the literature looking at detailed blood glucose monitoring in diabetic patients being treated for TB.
This study is planned as a case control study comparing 24 non-diabetic patients commencing TB treatment with 24 cases who have both TB and diabetes. Samples for post-dose TB drug levels will be taken at 2 time points at weeks 2, 8 and 16. These will be analysed via population pharmacokinetics to compare pharmacokinetic profiles between the 2 groups, with the hypothesis that the diabetic group will have a significantly lower exposure to TB drugs than the non-diabetic group. The diabetic group will also be asked to wear a continuous glucose monitor (blinded Dexcom) for 10 days at baseline and week 16, with data compared between the 2 time points.
Read the detailed description
This study has been designed as a case control trial analysed via population pharmacokinetic modelling, with the hypothesis that overall exposure to TB medications will be lower in the diabetic than the non-diabetic group.
Non-Diabetic group (controls):
This group will be asked to take their TB medications as usual, and return at weeks 2 and 8 (timed to fit with routine appointments) and week 16. On these days, participants will be asked to record a video or to call the study team when taking the TB medications, so that the time can be recorded, and will then attend later in the day for routine bloods (week 2 and 8) and trial bloods taken at the same time (trial bloods only at week 16). At each visit, consent will be checked, the participant will be weighed and current medications will be checked. Venepuncture will be carried out for scheduled blood tests and for TB drug levels. With the participant's consent, a further blood sample will be taken later in the day for TB drug levels in addition.
Diabetic group (cases):
The diabetic group will undertake the same visits as the control group, with 2 additional features. Part of the same blood samples taken for TB drug levels will be used to measure oral diabetes drug levels in participants established on oral diabetes medication. These participants will be asked to attend an additional visit after the baseline visit but prior to starting TB treatment. Participants will be asked to record (again via video or call to the team) the time the evening diabetes medications were taken, to omit the morning dose and then to attend for a blood sample for a baseline diabetes medication level. Diabetic patient will also wear a blinded continuous glucose monitor (CGM) for 10 days at baseline and at week 16. Participants will be trained, and at weeks 0 and 16, the study co-ordinator will apply the sensor and transmitter, which will be worn for the next 10 days. The data will then be analysed to compare week 0 with week 16.
Corticosteroid Subgroup:
As a pilot project, any patients commencing on TB therapy who are also receiving corticosteroids as part of TB treatment, will be approached to follow the sample schedule as the control group.
Blood samples will be processed within 30 minutes of venepuncture, and the serum fraction (which contains the medications) will be frozen to -20C at the on-site laboratory. Frozen samples will be transported to the testing laboratory in appropriately labelled containers. Batches of samples will be analysed using high performance liquid chromatography for TB and diabetes drug levels.
- Conditions
- Tuberculosis, Diabetes Mellitus
- Being tested
- TB Drug Levels
- Medical subject headings
- Tuberculosis, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TB Drug LevelsDiagnostic test
TB drug levels at 1-2 time points at weeks 2, 8 and 16
| Study group | Role | What they receive |
|---|---|---|
| Diabetic Group (Cases) | 1. Subject aged 18 years of age or over
2. Written, informed consent obtained.
3. New diagnosis of tuberculosis and starting on anti-tuberculosis treatment
4. Known diagnosis of diabetes or a raised IFCC HbA1c level (>= 48 mmol/mol) at the time of TB diagnosis Receives: Diagnostic Test: TB Drug Levels | |
| Non-Diabetic Group (Controls) | 1. Subject aged 18 years of age or over
2. Written, informed consent obtained.
3. New diagnosis of tuberculosis and starting on anti-tuberculosis treatment
4. IFCC HbA1c level < 48mmol/mol and no known diagnosis of diabetes Receives: Diagnostic Test: TB Drug Levels |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rifampicin/Isoniazid/Pyrazinamide Cmax 2 hours post-dose
To be measured via population pharmacokinetic modelling, with case group compared to control group.
Measured: 2, 8, 16 weeks as discussed above
Secondary outcomes (2)
Antidiabetic medication Cmax at baseline and 2 hours post dose
To be measured via population pharmacokinetic modelling, with baseline compared to weeks 2, 8 and 16.
Measured: Baseline, 2, 8 and 16 weeks as discussed above
Mean daily subcutaneous glucose measurement
Via CGM comparing baseline with week 16
Measured: Baseline and 16 weeks for 10 days each
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2022
- Study start1 Feb 2022
- Primary completion1 May 2023
- Study completionMay 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London North West Healthcare NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ann Sturdy, Principal investigator, LONDON NORTH WEST UNIVERSITY HEALTHCARE NHS TRUST
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05329415
- Sponsor's protocol ID
- v1 20.07.2021
- Status last verified
- Apr 2023
- First submitted
- 17 Sep 2021
- Last updated
- 7 Jun 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tuberculosis Drug Levels and Continuous Glucose Monitoring in Diabetic Patients
- ClinicalTrials.gov ID
- NCT05329415
- Acronym / sponsor ID
- v1 20.07.2021
- Conditions
- Tuberculosis, Diabetes Mellitus
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- London North West Healthcare NHS TrustUniversity, hospital or other
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- May 2024 (estimated)
- First posted
- 15 Apr 2022 (actual)
- 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.
Diabetes significantly increases the risk of developing active tuberculosis (TB). Diabetic patients who do develop TB have worse treatment outcomes and overall mortality. TB also worsens blood glucose control in diabetics, the mechanism of which is not well understood. The incidence of type 2 diabetes is rising globally, and consequently diabetes and TB co-infection is increasingly common, and improving outcomes in this cohort is of growing importance.
Low TB drug levels in diabetic patients have been postulated as a reason for these worse outcomes. There is however contradictory evidence in the literature that TB drug levels really are consistently and significantly lower in diabetics compared with non-diabetics. If this were shown to be the case, performing therapeutic drug monitoring in diabetic patients may be a straightforward way to improve outcomes. Improving blood glucose control may also lead to improved outcomes, however there is nothing previously in the literature looking at detailed blood glucose monitoring in diabetic patients being treated for TB.
This study is planned as a case control study comparing 24 non-diabetic patients commencing TB treatment with 24 cases who have both TB and diabetes. Samples for post-dose TB drug levels will be taken at 2 time points at weeks 2, 8 and 16. These will be analysed via population pharmacokinetics to compare pharmacokinetic profiles between the 2 groups, with the hypothesis that the diabetic group will have a significantly lower exposure to TB drugs than the non-diabetic group. The diabetic group will also be asked to wear a continuous glucose monitor (blinded Dexcom) for 10 days at baseline and week 16, with data compared between the 2 time points.
Detailed description
This study has been designed as a case control trial analysed via population pharmacokinetic modelling, with the hypothesis that overall exposure to TB medications will be lower in the diabetic than the non-diabetic group.
Non-Diabetic group (controls):
This group will be asked to take their TB medications as usual, and return at weeks 2 and 8 (timed to fit with routine appointments) and week 16. On these days, participants will be asked to record a video or to call the study team when taking the TB medications, so that the time can be recorded, and will then attend later in the day for routine bloods (week 2 and 8) and trial bloods taken at the same time (trial bloods only at week 16). At each visit, consent will be checked, the participant will be weighed and current medications will be checked. Venepuncture will be carried out for scheduled blood tests and for TB drug levels. With the participant's consent, a further blood sample will be taken later in the day for TB drug levels in addition.
Diabetic group (cases):
The diabetic group will undertake the same visits as the control group, with 2 additional features. Part of the same blood samples taken for TB drug levels will be used to measure oral diabetes drug levels in participants established on oral diabetes medication. These participants will be asked to attend an additional visit after the baseline visit but prior to starting TB treatment. Participants will be asked to record (again via video or call to the team) the time the evening diabetes medications were taken, to omit the morning dose and then to attend for a blood sample for a baseline diabetes medication level. Diabetic patient will also wear a blinded continuous glucose monitor (CGM) for 10 days at baseline and at week 16. Participants will be trained, and at weeks 0 and 16, the study co-ordinator will apply the sensor and transmitter, which will be worn for the next 10 days. The data will then be analysed to compare week 0 with week 16.
Corticosteroid Subgroup:
As a pilot project, any patients commencing on TB therapy who are also receiving corticosteroids as part of TB treatment, will be approached to follow the sample schedule as the control group.
Blood samples will be processed within 30 minutes of venepuncture, and the serum fraction (which contains the medications) will be frozen to -20C at the on-site laboratory. Frozen samples will be transported to the testing laboratory in appropriately labelled containers. Batches of samples will be analysed using high performance liquid chromatography for TB and diabetes drug levels.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diabetic Group (Cases) | – | Diagnostic Test: TB Drug Levels1. Subject aged 18 years of age or over 2. Written, informed consent obtained. 3. New diagnosis of tuberculosis and starting on anti-tuberculosis treatment 4. Known diagnosis of diabetes or a raised IFCC HbA1c level (>= 48 mmol/mol) at the time of TB diagnosis |
| Non-Diabetic Group (Controls) | – | Diagnostic Test: TB Drug Levels1. Subject aged 18 years of age or over 2. Written, informed consent obtained. 3. New diagnosis of tuberculosis and starting on anti-tuberculosis treatment 4. IFCC HbA1c level < 48mmol/mol and no known diagnosis of diabetes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants will be recruited from TB clinics at London North West University NHS Trust.
Key inclusion criteria (10 listed)
- Subject aged 18 years of age or over
- Written, informed consent obtained.
- New diagnosis of tuberculosis and starting on anti-tuberculosis treatment
- Known diagnosis of diabetes or a raised IFCC HbA1c level (>= 48 mmol/mol) at the time of TB diagnosis
- Subject aged 18 years of age or over
Key exclusion criteria (2 listed)
- Subject aged under 18 years
- Inability to give informed consent
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 |
|---|---|---|
| TB Drug LevelsTB drug levels at 1-2 time points at weeks 2, 8 and 16 | Diagnostic test | Diabetic Group (Cases), Non-Diabetic Group (Controls) |
Primary outcome
Rifampicin/Isoniazid/Pyrazinamide Cmax 2 hours post-dose
Time frame: 2, 8, 16 weeks as discussed above
To be measured via population pharmacokinetic modelling, with case group compared to control group.
2 secondary outcomes
Antidiabetic medication Cmax at baseline and 2 hours post dose
Time frame: Baseline, 2, 8 and 16 weeks as discussed above
Mean daily subcutaneous glucose measurement
Time frame: Baseline and 16 weeks for 10 days each
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2023.
- Individual participant dataSharing planned: Undecided
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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.
Ann Sturdy principal investigator
LONDON NORTH WEST UNIVERSITY HEALTHCARE NHS TRUST
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis and Diabetes Mellitus, run by London North West Healthcare NHS Trust at 1 site in United Kingdom.
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 10 inclusion and 2 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 7 Jun 2023. 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 Kingdom. 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rifampicin/Isoniazid/Pyrazinamide Cmax 2 hours post-dose (time frame: 2, 8, 16 weeks as discussed above). 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 7 Jun 2023.