Study of beta blockers for salt wasting in patients with brain TB
ISRCTN | ISRCTN16770388 |
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DOI | https://doi.org/10.1186/ISRCTN16770388 |
- Submission date
- 11/09/2025
- Registration date
- 26/09/2025
- Last edited
- 12/09/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Tuberculous meningitis (TBM) is a serious brain infection caused by tuberculosis. TBM can cause serious problems in the brain, including increase volume of cerebrospinal fluid (CSF) leading to enlargement of brain’s hollow cavities (ventricles), strokes (especially in younger people), and convulsions. One common complication in TBM is hyponatremia, which means low levels of sodium in the blood. This happens in about one in three TBM patients. There are many reasons why sodium levels can drop, including poor appetite, vomiting, diarrhea, certain medications, and other health issues. In the past, a condition called SIADH (a condition where the body makes too much of a hormone called ADH) was thought to be the main reason for low sodium in TBM patients, but newer studies suggest that cerebral salt wasting (CSW) - a problem where the body loses too much salt due to brain stress - might actually be more common. CSW may be linked to the body's stress response, especially when there is brain pressure, infection, or stroke. One chemical involved in this stress response is called catecholamine. High levels of this chemical can cause the body to lose too much salt and water. Some research has shown that a type of medication called a beta blocker (which lowers stress signals in the body) may help improve outcomes in patients with brain injuries or stroke. Propranolol is one such beta blocker. In this study, we are testing whether propranolol can safely and effectively help to correct the low sodium levels and fluid loss in people with TBM-related CSW. We will compare it to standard care in a group of patients chosen at random.
Who can participate?
Patients aged between 15 to 70 years with TBM admitted during 2022 and 2024 in a tertiary care centre in India were screened for CSW
What does study involve?
The patients were randomly allocated to propranolol or placebo (saccharine). The intervention group received propranolol 10 mg twice daily on day one, which increased to 20 mg from day 2. Propranolol was continued until 1 month irrespective of correction of serum sodium; thereafter, gradually tapered within 2 weeks. Placebo group received a saccharine tablet in the similar manner.
What are possible benefits and risks of participating?
Propranolol is a drug used for reducing stress and to suppress catecholamine induced injury. Low serum sodium and high urinary output due to CSW may have early correction following adjunctive propranolol treatment. Hyponatremia is an independent risk factor of death in intensive care unit. Early correction of sodium and volume loss may reduce death and improve outcome. Propranolol is a drug used in medical practice for long time. It has a side effect profile including slowing of heart rate and reduction in blood pressure. The pulse and blood pressure will be monitored closely and in case of such side effects, the drug will be withdrawn.
Where is the study run from?
Sanjay Gandhi Post Graduate Institute of Medical Sciences (India)
When is the study starting and how long is it expected to run for?
March 2022 to December 2024
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Jayantee Kalita, jkalita@sgpgi.ac.in, jayanteek@yahoo.com
Contact information
Public, Scientific, Principal Investigator
Department of Neurology, C-block
Sanjay Gandhi Post Graduate Institute of Medical Sciences
Raebareli Road
Lucknow
226014
India
0000-0002-6141-3592 | |
Phone | +91 (0)5222494177 |
jkalita@sgpgi.ac.in |
Study information
Study design | Investigator-initiated single center open-label randomized placebo-controlled trial |
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Primary study design | Interventional |
Secondary study design | Randomised controlled trial |
Study setting(s) | Hospital |
Study type | Treatment, Safety, Efficacy |
Participant information sheet | 47982_PIS.pdf |
Scientific title | Role of beta blockers in cerebral salt wasting in the patients with tuberculous meningitis: an open labelled randomized control trial |
Study acronym | BEST - TBM |
Study objectives | Primary objective: Number of days to normalize serum sodium Secondary objective: 1. Number of days to achieve positive fluid balance 2. Number of days to have 3 l urinary output 3. Mortality at 1 month 4. Side effects 5. Functional outcome was assessed at 3 and 6 months using a modified Rankin Scale (mRS), and categorized as good (mRS score <3) and poor (mRS score 3 to 6) |
Ethics approval(s) |
Approved 11/03/2022, Institutional Ethics Committee, Sanjay Gandhi Post Graduate Institute of Medical Sciences (Raebareli Road, Lucknow, 226014, India; +91 (0)522-2494918, +91 (0)522 2668017; iec@sgpgi.ac.in), ref: 2021-225-DM-122 |
Health condition(s) or problem(s) studied | Cerebral salt wasting syndrome in patients with tuberculous meningitis |
Intervention | Once the diagnosis of cerebral salt wasting syndrome was ascertained in the patients with tuberculous meningitis, the patients were randomized to propranolol or placebo (saccharine) using simple randomization with a 1:1 allocation ratio. The intervention group received propranolol 10 mg twice daily on day one, which increased to 20 mg from day two. Propranolol was continued until 1 month irrespective of correction of serum sodium; thereafter, gradually tapered within 2 weeks. The placebo group received saccharine tablet in the similar manner. |
Intervention type | Drug |
Pharmaceutical study type(s) | Dose response |
Phase | Phase II |
Drug / device / biological / vaccine name(s) | Propranolol |
Primary outcome measure | The number of days for normalization of serum sodium: serum sodium levels were measured every third day for up to 1-month post-randomization, at 1 month, 3 months and 6 months follow-up |
Secondary outcome measures | 1. Number of days to achieve 500 ml positive fluid balance (Intake- output >500 ml). Daily fluid balance (intake and output over 24 hours) was recorded to monitor fluid status. 2. Number of days to have <3 L urinary output. Daily fluid balance (intake and output over 24 hours) was recorded to monitor fluid status. 3. Mortality recorded at 1 month 4. Side effects recorded during hospitalization and at follow-up visits at 1 month, 3 months, and 6 months 5. Functional outcome assessed using a modified Rankin Scale (mRS) and categorized as good (mRS score < 3) and poor (mRS score 3 to 6) at 3 and 6 months |
Overall study start date | 11/03/2022 |
Completion date | 15/12/2024 |
Eligibility
Participant type(s) | Patient |
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Age group | Adult |
Lower age limit | 15 Years |
Upper age limit | 70 Years |
Sex | Both |
Target number of participants | 38 |
Total final enrolment | 38 |
Key inclusion criteria | Patients aged between 15 to 70 years with tuberculous meningitis and having cerebral salt wasting syndrome (CSW) Diagnostic criteria of tuberculous meningitis Essential criteria: The clinical features of meningitis (fever, headache, vomiting) for more than 2 weeks Supportive criteria: 1. Cranial imaging: CT/MRI evidence of excaudate, hydrocephalous, granulomas in isolation or in combination 2. Cerebrospinal fluid: cells 10-500/mmb, lymphocytic predominance, protein >1 g/liter 3. Evidence of extra CNS active tuberculosis 4. Exclusion of alternative diagnosis of meningitis The diagnosis of CSW was based on the following essential and supportive criteria Essential criteria, all are mandatory 1. Polyuria (>3 l/day for two consecutive days) 2. Serum sodium <135 mEq/L in two consecutive tests 24 hours apart 3. Absence of secondary causes of hyponatremia such as renal, hepatic or cardiac failure, endocrinal disorder, natriuretic drugs etc Supportive criteria: three out of five are needed 1. Clinical incidence of hypovolemia: dry skin, hypotension, tachycardia or postural hypotension 2. Consistent fluid deficit on intake output chart 3. Laboratory evidence of dehydration such as elevated hematocrit, hemoglobin, albumin and blood urea 4. Central venous pressure less than 6 cm of water 5. Urinary sodium more than 40 mEq/L or urine osmolality more than 300 mOsmol/L on two consecutive days |
Key exclusion criteria | 1. Patients with endocrinal disorder, organ (renal, liver, heart) failure, vasculities, renal tubular acidosis, malignancy, pregnancy, lactation, on chemotherapy, radiotherapy, inotrope, dopaminergic, antidopaminergic, diuretics, carbamazepine, mannitol or aminoglycosides 2. Above 70 years and below 15 years of age 3. Denial of consent 4. Patients requiring mechanical ventilation or cardiopulmonary resuscitation |
Date of first enrolment | 12/03/2022 |
Date of final enrolment | 15/12/2024 |
Locations
Countries of recruitment
- India
Study participating centre
Lucknow
226014
India
Sponsor information
University/education
Raebareli Road
Lucknow
226014
India
Phone | +91 (0)5222494177 |
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jkalita@sgpgi.ac.in | |
Website | http://www.sgpgims.org.in |
https://ror.org/01rsgrz10 |
Funders
Funder type
Other
No information available
Results and Publications
Intention to publish date | 12/12/2025 |
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Individual participant data (IPD) Intention to share | Yes |
IPD sharing plan summary | Available on request |
Publication and dissemination plan | Planned publication in a peer- reviewed journal |
IPD sharing plan | The datasets generated during and analysed during the current study will be available upon request from Jayantee Kalita (jkalita@sgpgi.ac.in, jayanteek@yahoo.com) |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
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Participant information sheet | 12/09/2025 | No | Yes | ||
Statistical Analysis Plan | 12/09/2025 | No | No |
Additional files
Editorial Notes
12/09/2025: Study's existence confirmed by the Institutional Ethics Committee, Sanjay Gandhi Post Graduate Institute of Medical Sciences.