Multicentric trial on the use of combined therapy of Thiamine and biotine in patients with Huntington´s disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

6 Jun 2024 → ongoing

Decision date (initial)

2024-06-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Instituto de Salud Carlos III (ISCIII)

External identifiers

EU CT number

2023-508637-14-00

EudraCT number

2019-004360-22

ClinicalTrials.gov

NCT04478734

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Others, Safety

To evaluate the safety and tolerability of oral combination therapy of thiamine with biotin in patients with HD.

Secondary objectives 6

1. Demonstrate an increase in the level of thiamine monophosphate (TMP) in CSF of combined oral thiamine and biotin therapy in patients with HD.
2. The evaluation of the effectiveness of treatment with combined oral therapy of thiamine and oral biotin in the neurodegeneration produced in HD.
3. Measurement of bradykinesia through quantitative movement measurement techniques.
4. Measurement of the change in the volume of the caudate nucleus, white matter and cortical thinning, comparing these values ​​with those described in prospective registries of patients with HD.
5. To evaluate the biological effect of oral T/B combination therapy on neurofilament levels in CSF of patients with HD.
6. To evaluate the biological effect on neuroimaging markers of progression in patients with HD of oral combination therapy of thiamine with biotin.

Conditions and MedDRA coding

Huntington´s disease.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adult patients with Huntington's disease manifested by motor symptoms (chorea, dystonia or bradykinesia) and/or neuropsychiatric symptoms; and genetic confirmation of a number of repetitions of the CAG triplet in the HTT gene (coding for HTT) greater than or equal to 39 repetitions.
2. Women of childbearing age must have a negative serum or urine pregnancy test result at the screening visit. Likewise, they must accept the use of adequate contraceptive methods at least 15 days prior to the screening visit, during the course of the clinical trial and at least 15 days after the last visit.
3. In men who have a partner of childbearing age, accept the use of contraceptive methods.
4. Ability to give informed consent and comply with the visits stipulated in the study.

Exclusion criteria 5

1. Clinically significant medical problems that, in the judgment of the investigators, may cause tissue damage to the CNS or limit its repair, or that may expose the patient to unjustified risk or harm, or cause the patient not to complete the study.
2. Pregnancy or breastfeeding, or planning to become pregnant or patients of childbearing age not undergoing birth control methods (recommended by the Clinical Trial Facilitation Group (CTFG): http://www.hma.eu/fileadmin/dateien/Human_Medicines/ 01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf).
3. Patients dependent on basic activities of daily living (ABDL) or with a degree of severe cognitive impairment that prevents participation/follow-up in the study (UHDRS, Unified Huntington Disease Rating Scale TFC < 7).
4. Patients with active psychosis at the time of clinical evaluation.
5. Advanced kidney failure.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Periodic clinical examination and anamnesis directed by a neurologist during in-person and remote visits.
2. The collection of adverse effects during the interviews of the in-person visits to assess tolerability.
3. Analytical monitoring with hematological and biochemical control (liver and kidney function) during the dose escalation period, with this periodic control subsequently every 3 months.

Secondary endpoints 8

1. Determination of thiamine levels (free, TMP and TTP) in CSF and blood of patients at the beginning of the study and after its completion.
2. Comparison of thiamine levels (free, TMP and TTP) between the start and end of the study in CSF and blood of HD patients.
3. Measurement of NfL (neurofilament light chain protein) levels in CSF.
4. The score obtained in the motor and TFC (Total Functional Capacity) section of the UHDRS (Unified Huntington's Disease Rating Scale) (Annex III).
5. Quantitative motor assessment, Q-motor: is based on three-dimensional position sensors and pre-calibrated force translators (digitometers, among others) for standardized movement registration. This measurement will be carried out on patients at the pre-selection visit, randomization (baseline) and the quarterly in-person visits.
6. Score on the quality of life scale (SF-36) (Annex IV).
7. Variation of the patient and examiner clinical global impression scale (CGI-SyC) (Annex V).
8. Measurement of the change in the volume of the caudate nucleus, white matter and cortical thinning, comparing these values ​​with those described in prospective registries of patients with HD.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Sponsor organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Address

Avenida De Manuel Siurot S/n

City

Sevilla

Postcode

41013

Country

Spain

Scientific contact point

Organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Contact name

Clara María Rosso Fernández

Public contact point

Organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Contact name

Clara María Rosso Fernández

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications