Clinical trial NCT04977557: Thiamine in Patients With Clinically Suspected Dry Beriberi
Official title: Efficacy of Thiamine in Patients With Clinically Suspected Dry Beriberi: An Open Labeled Hospital Bases Study in Bangladesh
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dry Beriberi
Keywords: Neuritic beriberi
Dry beriberi
thiamine efficacy
Lead sponsor: Chittagong Medical College
Sponsor class: OTHER
First posted: 2021-07-27
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Abstract Background: Thiamine deficiency related disorders are increasingly being reported in countries where polished rice is the main dietary constituents and diet is not balanced in calorie, protein and micronutrients contents. Thiamine deficiency often associated with a sensory-motor neuropathy (dry beriberi) without Wernicke's encephalopathy and cardiac dysfunction.

Objectives: The objective of our study will be to evaluate the efficacy of thiamine in patients with clinically suspected dry beriberi.

Methods: This study will be a prospective, open labeled, self-controlled clinical trial (quasi-experimental study) carried out in the Neurology and Medicine Ward of Chittagong Medical College Hospital from July 2018 to June 2019. Fifty-five (55) patients of suspected dry beriberi will be recruited as per inclusion and exclusion criteria. All patients will be given 200mg IV Thiamine Hydrochloride per day for 1 week, then oral Tab. Thiamine 100mg twice daily for remaining 11week. They will be evaluated clinically before treatment and followed up at the end of 1 week, 6 week and 12 week after treatment. Assessment will be done by some clinical parameters like leg swelling, muscle cramp, muscle power, squat test, sensory impairments, deep tendon reflexes and by Overall Neuropathy Limitations Scale (ONLS) Score. Pre and post test treatment data will be recorded in a pre-designed case record form. To determine whether any o the difference between pretreatment and post treatment values were statistically significant or not, either Friedman's test or Cochran's Q test will be used. Analysis will be performed with SPSS windows version 23 and statistical significance will be defined as P\<0.05 and confidence interval will be set at 95% level. Our study result is likely to sensitize the health professionals of this region about this neglected health issue by increasing awareness of the clinical spectrum of Thiamine Deficiency related Peripheral Neuropathy.

Detailed description: This Self-controlled Clinical Trial will be conducted in Department of Neurology and Department of Medicine of Chittagong Medical College Hospital (CMCH) during July 2018 to June 2019. A total of 55 patients of possible beriberi will be included based on inclusion criteria. Patients with isolated cardiac/wet beriberi and with other known causes of peripheral neuropathy such as Diabetic, hereditary, Demyelinating (GBS, CIDP), metabolic (hepatic/renal impairment), history of intake of drugs (e.g. INH, Ethambutol, Phenytoin, Metronidazole, Dapsone etc.) and toxins exposure (As ,Organo-phosphate Compound, Pb ,Hg except alcohol) were excluded from study.

Operational Definitions:

Risk factors: Imbalanced diet (diet poor in thiamine/rich in carbohydrate or anti-thiamine factors), malnutrition, alcoholism, Gastro-Intestinal surgery, chronic diarrhoea, chronic vomiting, pregnancy or history of recent delivery, chronic, diuretics use, renal dialysis, total parenteral nutrition.

Possible/suspected neuritic (dry) beriberi: Risk factors + at least 2 of the following signs:

1. Muscle weakness of upper and or lower limb (less than grade 5 power in MRC scale)
2. Positive sensory symptoms (burning, tingling or pain)
3. Objective sensory deficit (pain, touch, position, vibration sense )
4. Absent or reduced deep tendon reflexes
5. Positive squat test (unable to rise after squatting without help)
6. Leg swelling Probable neuritic (dry) beriberi: Above symptoms recovered after thiamine treatment.

Data collection Procedure: After selection of subjects, detailed history, clinical examination and all other Information regarding sociodemographic and clinical factors of neuritic beriberi will be taken in a prescribed case record form. Relevant investigations (CBC, Peripheral Blood Flim (PBF), Serum creatinine, serum electrolytes, Liver function test, fasting \& 2 hour after breakfast sugar. HbA1C, TSH, serum Vitamin B12, Chest X ray, ECG, Echocardiography, CSF study, Nerve Conduction Study will be performed to exclude differential diagnoses. Then therapeutic trial of Inj. Thiamine will be given IV for 1st week (200mg IV daily) then orally (tab. Thiamin 100mg bd) for 11 weeks. Patients will be followed up after 1, 6 and 12 week to see the response on the basis of some clinical parameters and Overall Neuropathy Limitations Scale (ONLS) score.

Statistical Analysis: Continuous data will be reported as the means ± SD or median and interquartile range. Qualitative or categorical data will be described as frequencies and proportions. The intention to treat analysis (ITT) analysis will be used to determine the statistical significance. Missing values will be replaced by the series means for this purpose. To determine whether any of the difference between pretreatment and post treatment values are statistically significant or not, either Friedman's test or Cochran's Q test will be used. Former test compares the quantitative variables and non-dichotomous qualitative variables and the later test compares the dichotomous qualitative/categorical variables. Statistical significance will be defined as P \< 0.05 and confidence interval will be set at 95% level.

Variables under study:

Primary Outcome Variable: Treatment response will be measured by Overall Neuropathy Limitation Scale (ONLS) score before and after treatment.

Secondary Outcome Variables: Comparison and Assessment of clinical features at presentation and after treatment: leg swelling, muscle cramp, muscle power (MRC grading), deep tendon reflexes, sensory impairments (tingling /burning /pain/ touch/ position /vibration), squat test.

This study has received approval from Ethical Review Committee of Chittagong Medical College and written informed concent.will be taken from all participants.

Eligibility criteria: Inclusion Criteria:

1. Any person admitted to CMCH as a Suspected thiamine deficiency related peripheral Neuropathy / Possible dry-beriberi:

   Risk factors + at least 2 of the following signs:

   Risk factors include Imbalanced diet (diet poor in thiamine/rich in carbohydrate or anti-thiamine factors), malnutrition, alcoholism, Gastrointestinal surgery, chronic diarrhoea, chronic vomiting, pregnancy or history of recent delivery, chronic. diuretics use, renal dialysis, total parenteral nutrition.
   1. Muscle weakness of upper and or lower limb (less than grade 5 power in MRC scale)
   2. Positive sensory symptoms (burning, tingling or pain)
   3. Objective sensory deficit (pain, touch, position, vibration sense )
   4. Absent or reduced deep tendon reflexes
   5. Positive squat test (unable to rise after squatting without help)
   6. Leg swelling
2. Age 18 years and above.

Exclusion Criteria:

1. Patients with isolated cardiac/wet beriberi.
2. Patient with known causes of peripheral neuropathy such as Diabetic, hereditary, Demyelinating (GBS, CIDP), metabolic (hepatic/renal impairment), drugs (e.g. Isoniazid, Ethambutol, Phenytoin, Metronidazole, Dapsone etc.) Toxin (As ,Organo-phosphate Compound (OPC), Pb ,Hg except alcohol) etc.
3. Patients refuse to participate.

Primary outcomes:
measure: change in Overall Neuropathy Limitation Scale (ONLS) score
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
Secondary outcomes:
measure: change in leg swelling
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
measure: change in muscle power
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
measure: change in muscle cramp
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
measure: change in deep tendon reflexes
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
measure: change in squat test
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
measure: change in pain sensation
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
measure: change in position sensation
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
measure: change in vibration sensation
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
measure: change in touch sensation
timeFrame: before treatment with Thiamine (baseline ) and after 1 week, 6week, 12 week of treatment
Other outcomes:
Locations:
city: Chittagong
country: Bangladesh
facility: Chittagong Medical College Hospital
Study officials:
affiliation: Thesis Student
name: Nayema Masrura, MD,MBBS
role: PRINCIPAL_INVESTIGATOR
References: