Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05329415 |
| Other study ID # |
v1 20.07.2021 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2022 |
| Est. completion date |
May 2024 |
Study information
| Verified date |
April 2023 |
| Source |
London North West Healthcare NHS Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical 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.
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.
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.
