The KHENERGYZE Study
- Conditions
- Mitochondrial MyopathiesMitochondrial EncephalomyopathiesMitochondrial DiseasesMELAS SyndromeMIDD
- Interventions
- Drug: Placebo
- Registration Number
- NCT04165239
- Lead Sponsor
- Khondrion BV
- Brief Summary
Mitochondrial diseases, estimated prevalence 1 in 4,300 adults, is caused by pathogenic mutations in genes finally encoding for mitochondrial proteins of the various enzyme complexes of the OXPHOS. Among these mutations, the 3243A\>G nucleotide change in the mitochondrially encoded transfer RNALeu(UUR) leucine 1 gene (MT TL 1) is the most prevalent one. The OXPHOS dysfunction resulting from such mutations leads to increased production of reactive oxygen species (ROS), ultimately leading to irreversible oxidative damage of macromolecules, or to more selective and reversible redox modulation of cell signaling that may impact (adult) neurogenesis.
Despite advances in the understanding of mitochondrial disorders, treatment options are extremely limited and, to date, largely supportive. Therefore, there is an urgent need for novel treatments. KH176, a new active pharmaceutical ingredient (API), is an orally bio-available small molecule under development for the treatment of these disorders (see Section 1.4). The current study will further evaluate the effect of KH176 in various cognitive domains and evaluate the effect of different doses of KH176 (See Section 1.5).
In view of the growing recognition of the importance of mitochondrial function in maintaining cognitive processes in the brain, as well as the understanding of the safety profile and pharmacokinetics of KH176 following the two clinical studies described above, a more detailed study is indicated of the effects of KH176 in various cognitive domains, using the confirmed safe and well-tolerated KH176 dose of 100 mg bid, as well as a lower dose of 50 mg bid. The primary objective is an evaluation of KH176 in the attention domain of cognitive functioning, as assessed by the visual identification test score of the Cogstate computerised cognitive testing battery.
- Detailed Description
For this study, a 3 x 3 crossover design will be applied, i.e., with 3 treatments, 3 sequences and 3 periods, employing a Latin square assignment. Using this design, each subject will function as his/her own control. This will reduce variability and thus increase the chances of observing true effects between treatment periods (effects of treatment compared to placebo). In each treatment period, assessments will be performed at baseline prior to dosing and post dosing, enabling a change from baseline analysis and enabling the possibility to compare baseline conditions for each treatment period. The treatment period in each treatment is 28 days (4 weeks), which is supported by the pre-clinical toxicology program. In mouse studies, a 4-week period was sufficient to observe clinically relevant effects.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 27
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment A KH176 Oral administration of 50 mg KH176 twice daily Treatment B KH176 Oral administration of 100 mg KH176 twice daily Treatment C Placebo Oral administration of matching placebo twice daily
- Primary Outcome Measures
Name Time Method Cognitive functioning: Attention One month The attention domain score of cognitive functioning, as assessed by the visual Identification Test of the Cogstate computerised cognitive testing battery
- Secondary Outcome Measures
Name Time Method Executive functioning One month The executive functioning domain score of cognitive functioning, as assessed by the Groton Maze Learning Test of the Cogstate computerised cognitive testing battery
Psychomotor function One month The psychomotor functioning domain score of cognitive functioning, as assessed by the Detection Test of the Cogstate computerised cognitive testing battery
Visual learning One month The visual learning domain score of cognitive functioning, as assessed by the One Card Learning Test of the Cogstate computerised cognitive testing battery
Verbal learning One month The verbal learning functioning domain score of cognitive functioning, as assessed by the International Shopping List Test of the Cogstate computerised cognitive testing battery
Number of headache days One month Self report diary
Pure Tone Audiometry (PTA) One month Standardized test measure individual hearing threshold levels
Working Memeory One month The working memory domain score of cognitive functioning, as assessed by the One Back Test of the Cogstate computerised cognitive testing battery
Beck Depression Inventory One month 21-question multiple-choice self-report inventory, for measuring the severity of depression
Cognitive Failure Questionnaire (CFQ) One month Questionnaire to evaluate subjective cognitive functioning.
Newcastle Mitochondrial Disease Scale for Adults (NMDAS) One month Semi-quantitative clinical rating scale designed for mitochondrial disease. The rating scale explores several domains: current function, system specific involvement, current clinical assessment and quality of life
University of Penn Smell Identification Test (UPSIT) One month Test to measure the individual's ability to detect odors at a suprathreshold level.
Test of Attentional Performance (TAP) One month Standardised test to evaluate alertness and mental flexibility
Hamilton Anxiety and Depression Score (HADS) One month Subject-reported outcome measure and comprises 14 items equally divided over the two subscales anxiety (HADS-A) and depression (HADS-D)
Neuro-QoL Fatigue Short Form (quality in life in neurological disorders) One month 8-item self assessment questionnaire evaluating the perception of fatigue and its impact in daily life activities
Trial Locations
- Locations (4)
Rigshospitalet, University of Copenhagen
🇩🇰Kopenhagen, Denmark
Friedrich-Baur Institut
🇩🇪München, Bayern, Germany
Radboud University Medical Center
🇳🇱Nijmegen, Netherlands
Institute for Ageing and Health Newcastle University
🇬🇧Newcastle upon Tyne, United Kingdom