Wernicke-Korsakoff SyndromePhase 4OpTInNCT02788552
Optimum Thiamine Intervention (OpTIn) Trial
A Phase 4 study testing Thiamine Hydrochloride in people with Wernicke-Korsakoff Syndrome, run by Menzies School of Health Research at 1 site in Australia.
Trial summary
Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. The primary cause of WKS is thiamine deficiency, and more than 90% of cases are reported in alcohol dependent patients because alcohol dependence predisposes… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Wernicke-Korsakoff Syndrome
- What is being tested?
- Thiamine Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 334 participants
- Where
- 1 siteAustralia
- Study dates
- Sep 2014to 1 Aug 2019
- Phase
- Phase 4
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged range 18-65 years
- History of heavy alcohol use AUDIT-C score >4 or consumption >60mg/day or >80mg/binge
Who cannot join
- Pregnant women
- Under the age of 18 or over 65 years old
- Known pre-existing neurological or cognitive impairment unrelated to thiamine deficiency or WKS
- Renal dialysis patients
- Sedated patients in ICU
Trial locations and contacts
1 site in 1 country.
Australia1 site
Alice Springs Hospital
Alice Springs, Northern Territory, 0810
About this study
Official title: Optimum Thiamine Intervention (OpT In) for Treatment and Prevention of Wernicke-Korsakoff Syndrome (WKS): A Randomised Controlled Trial
Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. The primary cause of WKS is thiamine deficiency, and more than 90% of cases are reported in alcohol dependent patients because alcohol dependence predisposes to severe nutritional deficiency. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. Whilst effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens. This project proposes to develop quality evidence for effective treatment of WKS in an Aboriginal setting.
Read the detailed description
Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. The primary cause of WKS is thiamine deficiency, and more than 90% of cases are reported in alcohol dependent patients because alcohol dependence predisposes to severe nutritional deficiency. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. Whilst effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens. This project proposes to develop quality evidence for effective treatment of WKS in an Aboriginal setting..
The need for evidence-based thiamine treatment protocols is of great clinical importance for two related reasons. First, in relation to acute symptomatic WKS, a failure to treat immediately or adequately may result in profound and often permanent cognitive and neurological disability. Secondly, the need for evidence-based treatment guidelines is greatly magnified when it is recognised that milder, subclinical WKS may be preventable with adequate thiamine treatment.
The aims of this study are to determine the optimal thiamine dose required for:
- Treatment of acute symptomatic WKS among Aboriginal and non-Aboriginal alcohol dependent patients.
- Reducing or preventing subclinical WKS-related brain damage in at-risk Aboriginal and non-Aboriginal alcohol-dependent patients.
Primary Hypotheses
- Among alcohol-dependent patients with acute symptomatic WKS, higher doses of parenteral thiamine (1500mg) will lead to greater improvements in specific cognition and neurological functions than lower doses (900mg or 300mg).
- Among alcohol-dependent patients that are at high risk for subclinical WKS-related brain damage, higher doses of parenteral thiamine (900mg) will lead to greater improvements in specific cognition and neurological functions compared to lower doses (300mg or 100mg).
Secondary Hypotheses
- Thiamine deficient patients will show poorer performance on cognitive and neurological measures.
- Patients with concurrent magnesium deficiency will show greater impairment at baseline.
- Nutritional risk and alcohol frequency will correlate with thiamine pyrophosphate levels.
- Number of previous admissions with thiamine supplementation in the past 3 months will correlate with thiamine pyrophosphate levels
- Conditions
- Wernicke-Korsakoff Syndrome
- Being tested
- Thiamine Hydrochloride
- Keywords
- Neurological, Diet and Nutrition, Mental Health
- Medical subject headings
- Korsakoff Syndrome, Neurologic Manifestations, Psychological Well-Being
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thiamine HydrochlorideDrug
Also called Vitamin B1, Thiamine Chloride, Aneurine Hydrochloride, B Complex Vitamin
Administered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins.
| Study group | Role | What they receive |
|---|---|---|
| Acute Symptomatic WKS- 300mg | Active comparator | Thiamine Hydrochloride 300mg daily (i.e. 100mg 3 times/day) for 5 days Receives: Drug: Thiamine Hydrochloride |
| Acute Symptomatic WKS - 900mg | Active comparator | Thiamine Hydrochloride 900mg daily (i.e. 300mg 3 times/day) for 5 days Receives: Drug: Thiamine Hydrochloride |
| Acute Symptomatic WKS - 1500mg | Active comparator | Thiamine Hydrochloride 1500mg daily (i.e. 500mg 3 times/day) for 5 days. Receives: Drug: Thiamine Hydrochloride |
| High-risk subclinical WKS- 100mg | Active comparator | Thiamine Hydrochloride 100mg once daily for 3 days. Receives: Drug: Thiamine Hydrochloride |
| High-risk subclinical WKS- 300mg | Active comparator | Thiamine Hydrochloride 300mg (i.e. 100mg 3 time/day) for 3 days Receives: Drug: Thiamine Hydrochloride |
| High-risk subclinical WKS - 900mg | Active comparator | Thiamine Hydrochloride 900mg daily (i.e. 300mg 3 times/day) for 3 days. Receives: Drug: Thiamine Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Standardised Cognitive assessment - RUDAS
Evaluate differences in cognitive outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days); and among patients at high risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); using Standardised cognitive assessment - Rowland Universal Dementia Assessment Scale (RUDAS).
Measured: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients
Standardised Cognitive assessment - CogState
Evaluate differences in cognitive outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days); and among patients at high risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); using CogState battery.
Measured: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients
Standardised Cognitive assessment - Story Memory Recall Test
Evaluate differences in cognitive outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days); and among patients at high risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); using Story Memory Recall test
Measured: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients
Standardised neurological examination
Evaluate differences in neurological outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days);and among patients at high-risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); Using Standardised neurological examination. Aggregated as either normal or abnormal.
Measured: Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients
Secondary outcomes (4)
Blood thiamine levels
Correlate changes in red cell thiamine test results (blood test) with cognitive (standardised cognitive assessments score) and neurological functioning (standardised neurological examination).
Measured: Days 1 and 5 for acute symptomatic patients; days 1 and 3 for at risk patients
Magnesium levels
Examine the impact of magnesium deficiency (magnesium blood test) on thiamine treatment response (cognition as measured by standardised cognitive assessments and thiamine pyrophosphate levels as measured by blood test).
Measured: Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients
Demographic factors
Assess independent predictors of WKS including nutritional factors, substance use history and demographic factors assessed by questionnaire items including Nutritional Risk Assessment and AUDIT-C.
Measured: Day 1
Readmission
Examine the impact of patient re-admission on red cell thiamine pyrophosphate levels (blood test) and cognitive and neurological functioning (standardised cognitive and neurological assessments)
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2016 (estimated)
- Study startSep 2014
- Primary completion30 May 2019
- Study completion1 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Wernicke-Korsakoff SyndromeStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 334 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menzies School of Health Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kylie Dingwall, PhD, Principal investigator, Menzies School of Health Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02788552
- Sponsor's protocol ID
- 2014-08-27_Version2.1
- Other IDs
- ACTRN12614000327684, Project Grant GNT1057968
- Acronym
- OpTIn
- Status last verified
- Aug 2019
- First submitted
- 26 Sep 2014
- Last updated
- 16 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimum Thiamine Intervention (OpT In) for Treatment and Prevention of Wernicke-Korsakoff Syndrome (WKS): A Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT02788552
- Acronym / sponsor ID
- OpTIn / 2014-08-27_Version2.1
- Conditions
- Wernicke-Korsakoff Syndrome
- Keywords
- Neurological, Diet and Nutrition, Mental Health
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 334 participants (actual)
- Lead sponsor
- Menzies School of Health ResearchUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- 30 May 2019 (actual)
- Study completion
- 1 Aug 2019 (actual)
- First posted
- 2 Jun 2016 (estimated)
- 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.
Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. The primary cause of WKS is thiamine deficiency, and more than 90% of cases are reported in alcohol dependent patients because alcohol dependence predisposes to severe nutritional deficiency. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. Whilst effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens. This project proposes to develop quality evidence for effective treatment of WKS in an Aboriginal setting.
Detailed description
Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. The primary cause of WKS is thiamine deficiency, and more than 90% of cases are reported in alcohol dependent patients because alcohol dependence predisposes to severe nutritional deficiency. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. Whilst effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens. This project proposes to develop quality evidence for effective treatment of WKS in an Aboriginal setting..
The need for evidence-based thiamine treatment protocols is of great clinical importance for two related reasons. First, in relation to acute symptomatic WKS, a failure to treat immediately or adequately may result in profound and often permanent cognitive and neurological disability. Secondly, the need for evidence-based treatment guidelines is greatly magnified when it is recognised that milder, subclinical WKS may be preventable with adequate thiamine treatment.
The aims of this study are to determine the optimal thiamine dose required for:
- Treatment of acute symptomatic WKS among Aboriginal and non-Aboriginal alcohol dependent patients.
- Reducing or preventing subclinical WKS-related brain damage in at-risk Aboriginal and non-Aboriginal alcohol-dependent patients.
Primary Hypotheses
- Among alcohol-dependent patients with acute symptomatic WKS, higher doses of parenteral thiamine (1500mg) will lead to greater improvements in specific cognition and neurological functions than lower doses (900mg or 300mg).
- Among alcohol-dependent patients that are at high risk for subclinical WKS-related brain damage, higher doses of parenteral thiamine (900mg) will lead to greater improvements in specific cognition and neurological functions compared to lower doses (300mg or 100mg).
Secondary Hypotheses
- Thiamine deficient patients will show poorer performance on cognitive and neurological measures.
- Patients with concurrent magnesium deficiency will show greater impairment at baseline.
- Nutritional risk and alcohol frequency will correlate with thiamine pyrophosphate levels.
- Number of previous admissions with thiamine supplementation in the past 3 months will correlate with thiamine pyrophosphate levels
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Acute Symptomatic WKS- 300mg | Active comparator | Drug: Thiamine HydrochlorideThiamine Hydrochloride 300mg daily (i.e. 100mg 3 times/day) for 5 days |
| Acute Symptomatic WKS - 900mg | Active comparator | Drug: Thiamine HydrochlorideThiamine Hydrochloride 900mg daily (i.e. 300mg 3 times/day) for 5 days |
| Acute Symptomatic WKS - 1500mg | Active comparator | Drug: Thiamine HydrochlorideThiamine Hydrochloride 1500mg daily (i.e. 500mg 3 times/day) for 5 days. |
| High-risk subclinical WKS- 100mg | Active comparator | Drug: Thiamine HydrochlorideThiamine Hydrochloride 100mg once daily for 3 days. |
| High-risk subclinical WKS- 300mg | Active comparator | Drug: Thiamine HydrochlorideThiamine Hydrochloride 300mg (i.e. 100mg 3 time/day) for 3 days |
| High-risk subclinical WKS - 900mg | Active comparator | Drug: Thiamine HydrochlorideThiamine Hydrochloride 900mg daily (i.e. 300mg 3 times/day) for 3 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Aged range 18-65 years
- History of heavy alcohol use AUDIT-C score >4 or consumption >60mg/day or >80mg/binge
Key exclusion criteria (5 listed)
- Pregnant women
- Under the age of 18 or over 65 years old
- Known pre-existing neurological or cognitive impairment unrelated to thiamine deficiency or WKS
- Renal dialysis patients
- Sedated patients in ICU
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 |
|---|---|---|
| Thiamine HydrochlorideAlso: Vitamin B1, Thiamine Chloride, Aneurine Hydrochloride, B Complex VitaminAdministered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins. | Drug | Acute Symptomatic WKS - 1500mg, Acute Symptomatic WKS - 900mg, Acute Symptomatic WKS- 300mg, High-risk subclinical WKS - 900mg, High-risk subclinical WKS- 100mg, High-risk subclinical WKS- 300mg |
Primary outcome
Standardised Cognitive assessment - RUDAS
Time frame: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients
Evaluate differences in cognitive outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days); and among patients at high risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); using Standardised cognitive assessment - Rowland Universal Dementia Assessment Scale (RUDAS).
Standardised Cognitive assessment - CogState
Time frame: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients
Evaluate differences in cognitive outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days); and among patients at high risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); using CogState battery.
Standardised Cognitive assessment - Story Memory Recall Test
Time frame: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients
Evaluate differences in cognitive outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days); and among patients at high risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); using Story Memory Recall test
Standardised neurological examination
Time frame: Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients
Evaluate differences in neurological outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days);and among patients at high-risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); Using Standardised neurological examination. Aggregated as either normal or abnormal.
4 secondary outcomes
Blood thiamine levels
Time frame: Days 1 and 5 for acute symptomatic patients; days 1 and 3 for at risk patients
Magnesium levels
Time frame: Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients
Demographic factors
Time frame: Day 1
Readmission
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2019.
- Individual participant dataSharing planned: No
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.
Kylie Dingwall, PhD principal investigator
Menzies School of Health Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Thiamine Hydrochloride in people with Wernicke-Korsakoff Syndrome, run by Menzies School of Health Research at 1 site in Australia.
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 2 inclusion and 5 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: finished, as of the sponsor's last update on 16 Aug 2019. 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 Australia. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Standardised Cognitive assessment - RUDAS (time frame: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients). The study lists 4 primary outcomes in all. 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 16 Aug 2019.