Huntington DiseasePhase 2HUNTIAMNCT04478734
Trial of the Combined Use of Thiamine and Biotin in Patients With Huntington's Disease
A Phase 2 study testing Moderate doses of Thiamine y Biotin and High doses of Thiamine y Biotin in people with Huntington Disease, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 3 sites in Spain.
Trial summary
Evaluate the safety and tolerability of combined oral thiamine with biotin therapy in patients with Huntington´s disease in mild to moderate stages and it is intended to evaluate the biological effect of the treatment in the central nervous system of these patients using as the main biomarker the increase in the level… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Huntington Disease
- What is being tested?
- Moderate doses of Thiamine y Biotin and High doses of Thiamine y Biotin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesSpain
- Study dates
- 12 Apr 2023to 30 Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- Patients of legal age with manifest Huntington's disease with motor symptoms (chorea, dystonia or bradykinesia) and/or neuropsychiatric; and genetic confirmation of a number of repetitions of the cytosine-adenine-guanine trinucleotide (CAG triplet) in the HTT gene (coding for HTT) greater than or equal to 39
- Patients should be capable of giving informed consent and attending the planned visit of the study.
- Women of childbearing age should obtain a negative result in the serum or urine pregnancy test at the screening visit. They must also accept the use of appropriate contraceptive methods during the course of the clinical trial and men who have a partner of childbearing age, accept the use of contraceptive methods
Who cannot join
- Medical comorbidities considered clinically significant by the clinical judgment of the investigators.
- Pregnancy or lactation
- Patients with HD dependents on the basic routine daily life activities (UHDRS TFC < 7) or a severe cognitive decline.
- Active psychosis at the moment of the screening evaluation.
- Severe renal failure.
- Patients previously treated with thiamine and/or biotin or enrolled in other HD clinical trial with oligonucleotide antisense (IONIS-HTTRX (RG6042).
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Spain3 sites, 3 recruiting
- Recruiting
Hospital Ramón y Cajal
Madrid
José Luis López-Sendón, MD, 0034 913368013, jlsendonmoreno@salud.madrid.org
- Recruiting
Hospital Universitario de San Sebastián
San Sebastián, San Sebastian, 20014
Javier Ruiz Martinez, MD, (0034) 943007027, javier.ruizmartinez@osakidetza.eus
- Recruiting
Virgen del Rocío Hospital
Seville, Seville, 41013
Pablo Mir Rivera, MD/PhD, +34955923039, pmir@us.es
Pablo Mir Rivera, MD/PhD
About this study
Official title: Multicentric Trial on the Use of Combined Therapy of Thiamine and Biotine in Patients With Huntington´s Disease
Evaluate the safety and tolerability of combined oral thiamine with biotin therapy in patients with Huntington´s disease in mild to moderate stages and it is intended to evaluate the biological effect of the treatment in the central nervous system of these patients using as the main biomarker the increase in the level of thiamine monophosphate (TMP) in cerebrospinal fluid (CSF) of these patients with Huntington Disease (HD) during a follow-up period of one year.
Our main hypothesis is that combined thiamine-biotin oral therapy is a secure and well-tolerated treatment, potentially capable of modifying the disease course or avoiding the progression of symptoms in early-stages HD patients
Read the detailed description
The assessment of the safety and tolerability of the combined oral thiamine and biotin therapy in patients with HD will be performed by:
- Periodic clinical examination and anamnesis directed by a neurologist during face-to-face and non-contact visits.
- The collection of adverse effects during interviews of face-to-face visits to assess tolerability.
- Analytical monitoring with hematological and biochemical control (hepatic and renal function) during the dose escalation period, subsequently being this periodic control every 3 months, from signature of informed consent until the end the follow up.
The evaluation of the biological efficacy of treatment with combined oral thiamine and biotin therapy in increasing thiamine monophosphate (TMP) levels in cerebrospinal fluid (CSF) of patients with HD is to be performed by:
- The determination of thiamine levels: free thiamine, TMP, and thiamine pyrophosphate (TTP) in CSF and blood of patients at the beginning and after the end of the study.
- Comparison of thiamine levels (free, TMP and TTP) between the start and the end of the study in CSF and serum of patients with HD.
The evaluation of the biological efficacy of the treatment with combined oral thiamine and oral biotin therapy in neurodegeneration produced in HD will be performed by:
- Measurement of neurofilament light chain protein (NfL) levels in CSF at the baseline visit and after the end of the treatment.
- The obtained score in the motor and Total Functional Capacity (TFC) section of the Unified Huntington's Disease Rating Scale (UHDRS).
- Measurement of bradykinesia through quantitative motion measurement techniques (Quantitative motor assessment, Q-motor). Q-motor assessment relies on three-dimensional position sensors and pre-calibrated force translators, for standardized movement recording. This measurement will be made to patients in the pre-selection visit, randomization, and quarterly face-to-face visits.
- Score on the quality of life scale (SF-36).
- Variation in the overall clinical impression scale of the patient and the examiner.
- Measurement of the change in the volume of the caudate nucleus, white matter, and cortical thickness, as well as in the change of the Combined cerebral atrophy score. Measurements of cerebral structures will be acquired on magnetic resonance imaging scans (3T) at the baseline visit and after the end of the treatment.
To determine the sample size required to examine secondary and exploratory objectives, we based our estimations on the published thiamine-biotin treatment effects in preclinical HD models, and on the reported differences in CSF thiamine levels between HD patients and healthy subjects (Pico S, et al. 2021). According to the previous results, it is expected that a medium-to-high effect size (0.6 ≤ Cohen's d ≥ 0.8) would be necessary to restore TPP, TMP and Free-thiamine levels in CSF after treatment. Based on the parameter choices, for a desired power of 0.80 and a Type I error rate of 0.05, we estimate that we would need 24 HD patients to detect a standardized mean difference of 0.6. Sample size analysis was conducted using GPower 3.1.9.7 software.
The demographic data collection as well as the information related to all the variables analyzed during the study will be done through an electronic data collection notebook. The notification of adverse effects, severity, and relationship with study medication will be done through an electronic data collection notebook.
All statistical analyses will be conducted using SPSS v.26.0. IBM software and R studio software package. Linear regression will be used when the variables are quantitative (eg, scale measurements, CSF thiamine or NfL levels, among others) controlling for age, sex, CAG repetitions and motor symptom severity (UHDRS and UHDRS-Total Functional Capacity) at baseline as potential confounding variables. Logistic or multinomial regression when the variables are groups (binary or multinomial).
We will examine the association between the severity of disease and CSF thiamine among HD patients by fitting a linear mixed model for each clinical measurement, with age, sex, CAG repetitions and disease severity (UHDRS-TFC) as the covariates.
Magnetic resonance imaging performed during the study will be processed with specific neuroimaging programs for volumetry, diffusion and cortical thickness.
- Conditions
- Huntington Disease
- Being tested
- Moderate doses of Thiamine y Biotin, High doses of Thiamine y Biotin
- Keywords
- thiamine and biotine, combination therapy
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Moderate doses of Thiamine y BiotinDrug
Also called moderate doses of combination therapy
Thiamine 600 mg every day + Biotin 150mg every day
High doses of Thiamine y BiotinDrug
Also called high doses of the combination therapy
Thiamine 1200 mg every day + Biotin 300mg every day
| Study group | Role | What they receive |
|---|---|---|
| Moderate doses | Experimental | moderate doses of combination therapy applying the minimum average dosage of thiamine and biotin used in patients with BTBGD Receives: Drug: Moderate doses of Thiamine y Biotin |
| High doses | Experimental | high doses of the combination therapy applying the average standard dosage of thiamine and biotin used in patients with BTBGD. Receives: Drug: High doses of Thiamine y Biotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events as assessed by clinical examination anamnesis and Analytical monitoring with hematological and biochemical control (hepatic and renal function)
Patient´s condition and emergence of comorbidity by clinical examination and anamnesis directed by a neurologist, by measuring of vital signs (blood pressure, heart rate,breath rate weight and height)
Measured: From signature of informed consent form, at all scheduled visits, to end of follow up week 52
Secondary outcomes (1)
The evaluation of the efficacy of treatment with combined oral thiamine and biotin therapy in increasing thiamine monophosphate (TMP) levels in CSF of patients with HD
Determination and comparison of thiamine levels (free, TMP and TTP) in CSF and blood at the beginning and the end of the treatment.
Measured: At baseline (week 0) and visit 8 (week 48)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2020
- Study start12 Apr 2023
- Primary completion30 Jun 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Huntington DiseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Collaborators
- Consorcio Centro de Investigación Biomédica en Red (CIBER)
- Responsible party
- Sponsor
- Investigators
- Pablo Mir Rivera, MD/PhD, Study director, Institute of Biomedicine of Seville (IBiS)Clara M. Rosso Fernández, Principal investigator, Virgen del Rocío University Hospital Research and Clinical Trials Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04478734
- Sponsor's protocol ID
- HUNTIAM
- Acronym
- HUNTIAM
- Status last verified
- Jan 2025
- First submitted
- 11 Feb 2020
- Last updated
- 25 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Once the study is completed and the data processed, the results will be shared
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentric Trial on the Use of Combined Therapy of Thiamine and Biotine in Patients With Huntington´s Disease
- ClinicalTrials.gov ID
- NCT04478734
- Acronym / sponsor ID
- HUNTIAM / HUNTIAM
- Conditions
- Huntington Disease
- Keywords
- thiamine and biotine, combination therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Collaborators
- Consorcio Centro de Investigación Biomédica en Red (CIBER)
- Study start
- 12 Apr 2023 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 21 Jul 2020 (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.
Evaluate the safety and tolerability of combined oral thiamine with biotin therapy in patients with Huntington´s disease in mild to moderate stages and it is intended to evaluate the biological effect of the treatment in the central nervous system of these patients using as the main biomarker the increase in the level of thiamine monophosphate (TMP) in cerebrospinal fluid (CSF) of these patients with Huntington Disease (HD) during a follow-up period of one year.
Our main hypothesis is that combined thiamine-biotin oral therapy is a secure and well-tolerated treatment, potentially capable of modifying the disease course or avoiding the progression of symptoms in early-stages HD patients
Detailed description
The assessment of the safety and tolerability of the combined oral thiamine and biotin therapy in patients with HD will be performed by:
- Periodic clinical examination and anamnesis directed by a neurologist during face-to-face and non-contact visits.
- The collection of adverse effects during interviews of face-to-face visits to assess tolerability.
- Analytical monitoring with hematological and biochemical control (hepatic and renal function) during the dose escalation period, subsequently being this periodic control every 3 months, from signature of informed consent until the end the follow up.
The evaluation of the biological efficacy of treatment with combined oral thiamine and biotin therapy in increasing thiamine monophosphate (TMP) levels in cerebrospinal fluid (CSF) of patients with HD is to be performed by:
- The determination of thiamine levels: free thiamine, TMP, and thiamine pyrophosphate (TTP) in CSF and blood of patients at the beginning and after the end of the study.
- Comparison of thiamine levels (free, TMP and TTP) between the start and the end of the study in CSF and serum of patients with HD.
The evaluation of the biological efficacy of the treatment with combined oral thiamine and oral biotin therapy in neurodegeneration produced in HD will be performed by:
- Measurement of neurofilament light chain protein (NfL) levels in CSF at the baseline visit and after the end of the treatment.
- The obtained score in the motor and Total Functional Capacity (TFC) section of the Unified Huntington's Disease Rating Scale (UHDRS).
- Measurement of bradykinesia through quantitative motion measurement techniques (Quantitative motor assessment, Q-motor). Q-motor assessment relies on three-dimensional position sensors and pre-calibrated force translators, for standardized movement recording. This measurement will be made to patients in the pre-selection visit, randomization, and quarterly face-to-face visits.
- Score on the quality of life scale (SF-36).
- Variation in the overall clinical impression scale of the patient and the examiner.
- Measurement of the change in the volume of the caudate nucleus, white matter, and cortical thickness, as well as in the change of the Combined cerebral atrophy score. Measurements of cerebral structures will be acquired on magnetic resonance imaging scans (3T) at the baseline visit and after the end of the treatment.
To determine the sample size required to examine secondary and exploratory objectives, we based our estimations on the published thiamine-biotin treatment effects in preclinical HD models, and on the reported differences in CSF thiamine levels between HD patients and healthy subjects (Pico S, et al. 2021). According to the previous results, it is expected that a medium-to-high effect size (0.6 ≤ Cohen's d ≥ 0.8) would be necessary to restore TPP, TMP and Free-thiamine levels in CSF after treatment. Based on the parameter choices, for a desired power of 0.80 and a Type I error rate of 0.05, we estimate that we would need 24 HD patients to detect a standardized mean difference of 0.6. Sample size analysis was conducted using GPower 3.1.9.7 software.
The demographic data collection as well as the information related to all the variables analyzed during the study will be done through an electronic data collection notebook. The notification of adverse effects, severity, and relationship with study medication will be done through an electronic data collection notebook.
All statistical analyses will be conducted using SPSS v.26.0. IBM software and R studio software package. Linear regression will be used when the variables are quantitative (eg, scale measurements, CSF thiamine or NfL levels, among others) controlling for age, sex, CAG repetitions and motor symptom severity (UHDRS and UHDRS-Total Functional Capacity) at baseline as potential confounding variables. Logistic or multinomial regression when the variables are groups (binary or multinomial).
We will examine the association between the severity of disease and CSF thiamine among HD patients by fitting a linear mixed model for each clinical measurement, with age, sex, CAG repetitions and disease severity (UHDRS-TFC) as the covariates.
Magnetic resonance imaging performed during the study will be processed with specific neuroimaging programs for volumetry, diffusion and cortical thickness.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Moderate doses | Experimental | Drug: Moderate doses of Thiamine y Biotinmoderate doses of combination therapy applying the minimum average dosage of thiamine and biotin used in patients with BTBGD |
| High doses | Experimental | Drug: High doses of Thiamine y Biotinhigh doses of the combination therapy applying the average standard dosage of thiamine and biotin used in patients with BTBGD. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients of legal age with manifest Huntington's disease with motor symptoms (chorea, dystonia or bradykinesia) and/or neuropsychiatric; and genetic confirmation of a number of repetitions of the cytosine-adenine-guanine trinucleotide (CAG triplet) in the HTT gene (coding for HTT) greater than or equal to 39
- Patients should be capable of giving informed consent and attending the planned visit of the study.
- Women of childbearing age should obtain a negative result in the serum or urine pregnancy test at the screening visit. They must also accept the use of appropriate contraceptive methods during the course of the clinical trial and men who have a partner of childbearing age, accept the use of contraceptive methods
Key exclusion criteria (6 listed)
- Medical comorbidities considered clinically significant by the clinical judgment of the investigators.
- Pregnancy or lactation
- Patients with HD dependents on the basic routine daily life activities (UHDRS TFC < 7) or a severe cognitive decline.
- Active psychosis at the moment of the screening evaluation.
- Severe renal failure.
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 |
|---|---|---|
| Moderate doses of Thiamine y BiotinAlso: moderate doses of combination therapyThiamine 600 mg every day + Biotin 150mg every day | Drug | Moderate doses |
| High doses of Thiamine y BiotinAlso: high doses of the combination therapyThiamine 1200 mg every day + Biotin 300mg every day | Drug | High doses |
Primary outcome
Incidence of Treatment-Emergent Adverse Events as assessed by clinical examination anamnesis and Analytical monitoring with hematological and biochemical control (hepatic and renal function)
Time frame: From signature of informed consent form, at all scheduled visits, to end of follow up week 52
Patient´s condition and emergence of comorbidity by clinical examination and anamnesis directed by a neurologist, by measuring of vital signs (blood pressure, heart rate,breath rate weight and height)
1 secondary outcome
The evaluation of the efficacy of treatment with combined oral thiamine and biotin therapy in increasing thiamine monophosphate (TMP) levels in CSF of patients with HD
Time frame: At baseline (week 0) and visit 8 (week 48)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2025.
- Individual participant dataSharing planned: Yes. Once the study is completed and the data processed, the results will be shared
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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.
Pablo Mir Rivera, MD/PhD study director
Institute of Biomedicine of Seville (IBiS)
Clara M. Rosso Fernández principal investigator
Virgen del Rocío University Hospital Research and Clinical Trials Unit
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Moderate doses of Thiamine y Biotin and High doses of Thiamine y Biotin in people with Huntington Disease, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 3 sites in Spain.
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 3 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pablo Mir Rivera, MD/PhD (+34 955923039, pmir@us.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events as assessed by clinical examination anamnesis and Analytical monitoring with hematological and biochemical control (hepatic and renal function) (time frame: From signature of informed consent form, at all scheduled visits, to end of follow up week 52). 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 25 Feb 2025.