Clinical Research Directory

Study to Evaluate the Pharmacodynamics, Safety and Efficacy of SKY-0515 in Participants With Huntington's Disease

The goal of this clinical trial is to test if the drug SKY-0515, an oral medication, can lower harmful proteins linked to Huntington's Disease (HD) and improve the symptoms of participants with HD. This study includes men and women aged 25 and older who have HD confirmed by genetic testing and meet certain requirements for physical ability and independence.

Creatine and Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation Plus Home-Based Exercise for Sarcopenia in Huntington's Disease

Huntington's disease (HD) is a rare neurodegenerative disorder in which accelerated loss of muscle mass, strength and autonomy (physical frailty and sarcopenia) contributes to functional decline. This randomized, double-blind, placebo-controlled, four-arm parallel trial will include adults with HD and physical frailty/sarcopenia. All participants will follow a 12-week individualized, home-based multicomponent exercise program (VIVIFRAIL-based, with weekly remote monitoring) and will be randomized 1:1:1:1 to placebo, creatine (CRE), beta-hydroxy-beta-methylbutyrate (HMB) or combined CRE+HMB. The study will test whether combined CRE+HMB produces synergistic improvements in functional capacity, neuromuscular performance, body composition, cognition and quality of life, and will use multi-omic profiling (circulating and extracellular-vesicle microRNAs, plasma proteomics and genetics) to identify mechanisms and predictive signatures of response. Durability of effects will be assessed 6 months after the end of the intervention.

Pridopidine Phase 3 Study in Huntington's Disease

The goal of this clinical trial is to learn if pridopidine can slow the clinical decline of Huntington's Disease (HD) in adult participants. It will also inform about the safety of pridopidine. The main questions the study aims to answer are: Does pridopidine slow the overall worsening of HD over 1 year? Does pridopidine slow the worsening of specific aspects of HD over 1 year, namely the clinical progression, the ability to perform daily life activities (functional capacity), the mind's ability to process information (cognition), working of the muscles (motor function), and quality of life? Researchers will compare the drug pridopidine to a placebo (a look-alike substance that contains no drug) to see if pridopidine works better than placebo to treat HD. During the first year of the study, participants will have the same chance to receive either pridopidine or placebo. Participants will: Take 1 pridopidine or placebo capsule twice daily for 12 months. Visit the clinic 6 times within 1 year for checkups and tests. All participants who complete this 1-year placebo-controlled study period will roll over into an additional 2-year study period during which all participants will receive pridopidine treatment, including participants who had received placebo during the first year. During this additional 2-year treatment period participants will visit the clinic a total of 6 times for checkups and tests.

Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders

Cell-free fetal DNA (cffDNA) is present in the maternal blood from the early first trimester of gestation and makes up 5%-20% of the total circulating cell-free DNA (cfDNA) in maternal plasma. Its presence in maternal plasma has allowed development of noninvasive prenatal diagnosis for single-gene disorders (SGD-NIPD). This can be performed from 9 weeks of amenorrhea and offers an early, safe and accurate definitive diagnosis without the miscarriage risk associated with invasive procedures. One of the major difficulties is distinguishing fetal genotype in the high background of maternal cfDNA, which leads to several technical and analytical challenges. Besides, unlike noninvasive prenatal testing for aneuploidy, NIPD for monogenic diseases represent a smaller market opportunity, and many cases must be provided on a bespoke, patient- or disease-specific basis. As a result, implementation of SGD-NIPD remained sparse, with most testing being delivered in a research setting. The present project aims to take advantage of the unique French collaborative network to make SGD-NIPD possible for theoretically any monogenic disorder and any family.

Multi-Modal Digital Monitoring of Disease Symptoms Huntington's Disease

The objective of the study is to validate the use of wearable sensors and digital health technologies for monitoring disease activity in Huntington's Disease (HD). Healthy subjects, as well as subjects with documented diagnosis of HD will be screened and recruited at University of Rochester Medical Center and Vanderbilt University Medical Center to participate in this 12-month observational study. There will be a total of 5 visits every approximately 3 months. In each study visit, participants will complete several Patient Reported Outcomes (PROs), Clinical Reported Outcomes, complete a series of Digital Assessments (Speech, Cognitive, Motor, and Finger Tapping). Participants will be provided with a pendant, wrist, and ankle sensors to monitor their daily physical activities for 7 days after each study visit. Participants will also be provided with a tablet to complete digital assessments (Speech, Cognitive, Motor, and Finger Tapping) on monthly basis at home.

A Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease

The purpose is to assess safety and tolerability of votoplam and to determine whether votoplam slows disease progression in patients with early symptomatic Huntington's disease (HD) compared to the control arm. HTT227 - current compound code (former code is PTC518 from PTC Therapeutics), HTT227 is Novartis code under Novartis sponsorship.

Promoting Goals-of-Care Discussions for Patients With Memory Problems and Their Caregivers

The goal of this clinical trial is to improve communication among clinicians, patients with memory problems, and their family members. We are testing a way to help clinicians have better conversations to address patients' goals for their healthcare. To do this, we created a simple, short guide called the "Jumpstart Guide." The goal of this research study is to show that using this kind of guide is possible and can be helpful for patients and their families. Patients' clinicians may receive a Jumpstart Guide before the patient's clinic visit. Researchers will compare patients whose clinician received a Jumpstart Guide to patients whose clinician did not receive a guide to see if more patients in the Jumpstart Guide group had conversations about the patient's goals for their healthcare. Patients and their family members will also be asked to complete surveys after the visit with their clinician.

An Open Label Study of ANX005 in Participants With, or at Risk for, Manifest Huntington's Disease

This study is a multi-center, open-label study of intravenous (IV) ANX005 in participants with, or at risk for, manifest Huntington's Disease (HD).

A Safety and Pharmacokinetics Trial of VO659 in SCA1, SCA3 and HD

The goal of this first-in-human clinical trial is to assess the safety and tolerability of four doses of a new study drug called VO659 in people with genetic disorders called spinocerebellar ataxia type 1, type 3 or Huntington's disease. Another aim is to determine the concentrations of the study drug in the cerebral spinal fluid and blood after single and multiple doses. Study drug will be administered by lumbar intrathecal bolus injections.

Digital Measures for Clinical Trial Endpoints in Huntington's Disease

MEND-HD is a longitudinal study evaluating the feasibility of passive monitoring of gait and chorea in patients with HD and the meaningfulness of these outcomes for patients with HD and their care partners/support persons. Participants will take part in four virtual visits with study investigators to answer survey questions on movement and cognition, perform in-home movement assessments, and take part in an interview regarding the meaningfulness of gait and chorea in their daily lives. Participant and care partner interviews will be used for symptom mapping and qualitative data analysis to assess the relevance and impact of the targeted symptoms on the participant's daily life. The study may be extended to 3 years to include yearly visits.

Gene Therapy Development and Validation for Huntington's Disease Fibro TG-HD

Huntington's disease is a rare and fatal monogenic neurodegenerative disorder whose molecular origin is an expansion of CAG triplets within the first exon of the Huntingtin gene. Although a growing number of emerging therapies are in clinical trials, there are no proven neuroprotective or curative treatments approved by the health authorities, as they have not yet demonstrated any real therapeutic benefit or absence of toxicity. Trans-splicing gene therapy is defined as the correction of a mutated endogenous pre-messenger RNA by a therapeutic exogenous pre-messenger RNA. Trans-splicing is a suitable alternative approach, since it is capable of allelic selectivity and replacement of mutated sequences by the wild-type one, criteria that no therapy tested to date meets. This project involves the therapeutic validation of trans-splicing of Huntingtin gene transcripts, and will evaluate its therapeutic effects in vitro, into primary fibroblast cell lines derived from skin biopsies of Huntington's disease patients.

Sociodemographic Factors and Criminal Behaviour Preceding Neurodegenerative Disease - Retrospective Register Study

In this retrospective register study, clinically classified individuals with neurodegenerative disease from the years 2010-2021 will be verified from the clinical records from KUH and Oulu University Hospital (OUH). Based on the Finnish social security number, these individuals will be linked to the the national registers of Statistics Finland and Finnish Social and Health Data Permit Authority Findata including incomes, sociodemographic factors, education, occupation, criminal records as well as to the national registers including the bought pharmaceuticals, comorbidities and causes of death. For each study case, 10 randomly selected control cases, matched with age, sex and geographical area, will be used. The aim of the study is to examine: * 1\) The prevalence of criminal and other disruptive behaviour in groups of different neurodegenerative diseases prior to and after the diagnosis * 2\) Changes in employment, residency,income, and marital status prior to and after the neurodegenerative disease diagnosis * 3\) Hospital diagnoses and reimbursable drugs prior to and after the diagnosis * 4\) Causes of death in patients with neurodegenerative disease to study excess mortality of the patients

GENERATION HD2. A Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen Compared With Placebo in Participants With Prodromal and Early Manifest Huntington's Disease

This study will evaluate the safety, biomarkers, and efficacy of tominersen compared with placebo in participants with prodromal and early manifest Huntington's Disease (HD).

Impact of Deutetrabenazine on Functional Speech and Gait Dynamics in Huntington Disease

Examine the effects of deutetrabenazine on functional speech and gait impairment

Proof of Concept of an Anaplerotic Study Using Brain Phosphorus Magnetic Resonance Spectroscopy in Huntington Disease

The purpose of this project is to study the efficacy of an anaplerotic treatment on brain energy profile evolution at an early stage of the Huntington disease.

Frequency of Selected Single Nucleotide Polymorphisms in Huntington Disease Gene Expansion Carriers

For participation in this epidemiological study, a single-day visit at the study site is required. Participants will be recruited from Huntington Disease clinics, and they will be asked to answer questions regarding their demographics, including sex, age, race and ethnicity, and their medical and medication history. At the end of the visit, a blood sample will be drawn to allow testing with a sequencing assay that is specifically designed for phasing single nucleotide polymorphisms (SNPs) on the wild-type Huntington (wtHTT) and mutant Huntington (mHTT) alleles.

Modification of Threat Interpretation Bias to Reduce Anxiety in Neurodegenerative Movement Disorders (Aim 3)

The purpose of this study is to assess preliminary efficacy of a tailored cognitive bias modification for interpretation (CBM-I) app for reducing anxiety in Huntington's disease and Parkinson's disease.

Gait Analysis in Neurological Disease

The purpose of this study is to investigate whether speed-dependent measures of gait (so called gait signatures) can be identified in patients with neurological conditions that affect gait, particularly in subjects with parkinsonian disorders.

Group Drum-Based Music Therapy Intervention for Parkinson's Disease/Huntington's Disease

Participants in this study (18-89 years) with Parkinson's disease or Huntington's disease receive drum classes twice a week for 12 weeks (24 lessons). All participants also participate in study visits for assessments before the beginning of the study, at the 6 week mark, at the 12 week mark and at the 18 week mark so that the investigators can assess the short and long term effects of drum classes on hand dexterity, upper extremity function and well-being.

Research of Biomarkers in Parkinson Disease

The main goal of the GENEPARK consortium is to employ innovative haemogenomic approaches to determine gene expression profiles specific for genetic and idiopathic Parkinson's disease (PD) patients. These gene expression signatures will be utilised clinically as non-invasive diagnostic tests for PD. The sensitivity of the newly developed diagnostic test will be determined by extensive validations on an independent cohort of PD patients, whereas the specificity will be assessed by testing patients with atypical parkinsonisms, including multiple system atrophy, progressive supranuclear palsy and diffuse Lewy body disease. In order to test the specificity of the diagnostic set in other disorders that affect basal ganglia, Huntington's disease and dopa responsive dystonia patients will be analysed. The second objective of the proposal is to determine correlations between gene expression signatures and different stages of PD and thus provide the basis for early diagnosis and monitoring of disease progression. These changes in blood gene expression will be correlated with alterations detected by neuroimaging in the brain of PD patients. Such combinations of molecular and morphological markers of disease may ultimately facilitate the selection and monitoring of neuroprotective therapies for PD. Finally, GENEPARK aims to develop new bioinformatic software tools for selection of genomic biomarkers using microarray data. A set of established computational tools will be applied and novel methods, some of them based on mechanistic modelling of the neurodegenerative diseases, will be developed in order to study the advantages and limitations of the different methodologies. With special emphasis on the careful clinical selection of patients and sufficient power regarding patient numbers, as well as extensive quality control and validation of the data, GENEPARK aims to develop a standardised approach to development and validation of haemogenomic biomarkers of disease.

A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD)

The primary goal of this study is to evaluate the safety and pharmacodynamic effects of PTC518 compared with placebo in participants with HD.

Dance and Huntington Disease

In this project investigators will evaluate the benefits of contemporary dance training using a comprehensive test battery combining standard neuropsychological batteries, psychological questionnaires on emotion, empathy and quality of life, structural magnet-resonance tomography (MRI), as well as psychophysical tests on movement recognition and agency, the sense of being in control of one's own movement. For 10 years now two experienced dancer-choreographers lead dance workshops for people with Huntington's Disease (HD) and their family and caregivers in Paris. This project will evaluate objectively the effects these workshops have, by assessing a new group of 18 patients and their partners and caregivers before and after 8 month of weekly dance training. People with HD are troubled by involuntary movements, of which they are however not accurately aware, but moreover they become impaired at recognising instrumental actions in others. It is well known that observing somebody else's action and executing the same action rest on a common neural network. This might mean that improving one's own action execution can improve the observation and understanding of others' actions in turn. Here, investigators will investigate both the impact the movement impairments caused by HD might have on patients themselves as well as on their partners and caregivers, as a consequence of the fact that own and other action representations are shared. After 8 months of contemporary dance training, both groups will be tested again, in order to establish if both action execution (self) and perception (in others) have improved. Other recent psychophysics and brain imaging experiments have demonstrated how the sense of agency is composed from external cues (for example sound) of the consequences of movements, and from internal sensorimotor information that result from the action plan. Importantly, in HD the latter input might be impaired, but this has never been systematically tested. Making use of a psychophysics paradigm disentangling the two cues to agency investigators first monitor the sense of their own movement in HD, and further assess the changes in agency and in the role of these cues to agency after eight months of contemporary dance practice. Finally investigators will monitor the structural brain changes accompanying this progress, comparing the brain before and after regular dance practice and correlating action recognition psychophysics measures of agency with these changes. In sum, this project has a double impact. Firstly it will scientifically evaluate the impact of dance on the normal but especially the brain affected by a neurodegenerative disease that causes movement impairments, and establish its effect on behaviour and wellbeing. Secondly it will evaluate in patient partners and caregivers how they represent the patients' as well as their own movements and how this changes with dance practice.

A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease

In the study the investigators plan to include 100 early affected HD patients (5 ≤ UHDRS ≤ 40) in a randomized, double-blind, controlled study in 2 centers (France and the Netherlands). Patients will receive either triheptanoin at 1g/kg of body weight per day (n = 50), or a control oil (n = 50) at 1g/kg of body weight per day for 6 months followed by an open label phase using triheptanoin for another 6 months. Efficacy of triheptanoin will be evaluated by measurements of caudate volume using volumetric magnetic resonance imaging. Clinical improvement will be evaluated by brain energy metabolism quantification as evaluated by the ratio of inorganic phosphate/phosphocreatine, during visual stimulation, using 31P-MRS, UHDRS, TFC, and PBA-S scores as well as performance on the neuropsychological battery. Patient quality of life will be evaluated with the SF-36 questionnaire before and after treatment; biological tolerance and compliance will be evaluated by routine biochemical blood tests, plasma and urine measurements of triheptanoin oil derivatives and patient report.

The Safety and Tolerability Study With ER2001 Intravenous Injection Repetitive Treatment in Adults With Early Manifest Huntington's Disease.

This is an open label, dose escalation clinic trial to evaluate safety, tolerability and pharmacokinetics with ER2001 Intravenous Injection repetitive treatment in Huntington's Disease patients who Completed Study ER2001-001（NCT06024265）. Furthermore, pharmacodynamics in particular target engagement, and clinical signs of efficacy will be assessed. This study will evaluate increasing doses of ER2001 in sequential cohorts. ER2001 was escalated over 3 dose levels . The planned duration of this additional treatment is 6 weeks for one course.