The FELL-HD Trial

A trial to assess the tolerability and feasibility of using felodipine to upregulate autophagy as a treatment for Huntington’s Disease


Research summary

Huntington’s disease (HD) is a progressive, genetic, neurodegenerative disorder that affects approximately 5,700 people in the UK with 5 times as many at risk of having inherited the gene. Clinical features typically emerge at the height of normal adult working life, namely between 30-50 years old, and include motor dysfunction, neuropsychiatric disturbances and cognitive difficulties. The disease runs a progressive course over about 20 years to death. There are currently only limited symptomatic therapies for HD, and these largely target only the motor features. There is therefore an urgent need for disease-modifying agents for patients with HD.


The major pathological problem in HD relates to the production of abnormal huntingtin, so called mutant huntingtin (mHTT), which over time aggregates and causes neuronal cells to dysfunction and then die. One way to try and stop HD from progressing is to increase (upregulate) clearance of mHTT from cells. One normal intracellular pathway that clears this (and any abnormal) protein is called autophagy.


We and others screened a group of existing drugs (that have been approved clinically for other indications) to identify drugs which were able to induce autophagy and which may be suitable for treating neurodegenerative diseases in patients.


From this review, felodipine was selected as the most suitable candidate for further assessment. Felodipine was shown in animal models to upregulate the autophagy process. Furthermore, felodipine is a commonly used antihypertensive drug which is typically administered long-term and is well-tolerated with modest side effects. It is also a cheap agent. Thus, if it induces autophagy in human brains, this drug may provide an economical and safe therapy that would have utility in many neurodegenerative diseases not just HD.


This trial has been designed to test the safety and tolerability of different doses of felodipine in patients with early-stage HDThis trial aims to test the safety and tolerability of felodipine in patients with early-stage HD using a range of dose levels.


Main inclusion criteria

  • Have given written informed consent
  • Be male or female, aged 35 to 70 years (inclusive)
  • Be a fluent English speaker, as assessed by the trial team during the screening visit, to enable completion of the cognitive assessments
  • Have early disease, as defined by a Unified Huntington’s disease Rating Scale (UHDRS) total functional capacity (TFC) score ≥ 9
  • Have a diagnostic confidence level (DCL) of ≥ 2

Main exclusion criteria

  • Participant has dementia (as defined by MMSE < 24 and/or ACE-III < 82) or lacks capacity to consent for themselves
  • Significant co-morbidities which, in the opinion of the Principal Investigator (PI), precludes inclusion in the trial
  • Ongoing medical or psychiatric condition that is not, in the opinion of the PI, adequately managed
  • Vital sign abnormality which, in the opinion of the PI, precludes inclusion in the trial including symptomatic hypotension
  • Poorly controlled features of HD, as indicated by a change in HD medication within 3 months of screening
  • contraindications to felodipine, including taking any medication known to significantly interact with felodipine. 
  • Participant is currently taking a calcium channel blocking anti-hypertensive medication or has taken a calcium channel blocking anti-hypertensive medication within 12 weeks of the screening visit
  • Known allergy to felodipine, any other dihydropyridine (due to theoretical risk of cross-hypersensitivity), or excipients of felodipine tablets
  • Presence of rare hereditary problem of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption as the tablet contains lactose
  • Participant is currently taking felodipine or has taken felodipine within 12 weeks of the screening visit
  • Female participant of childbearing potential who is unwilling or unable to use one highly effective method of contraception during the trial (as outlined in protocol section 11.11.1), as felodipine is not recommended to be taken during pregnancy (as per the BNF).
  • Female participant who is pregnant or breastfeeding
  • Participant has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks prior to the screening visit, or was enrolled in an interventional investigational trial within 4 weeks prior to screening
  • Any other significant disease, disability or investigation result which, in the opinion of the PI, may either put the participant at risk, or may influence the result of the trial, or the participant’s ability to participate in the trial

Funders and sponsors

Funders: UK DRI and NIHR Cambridge BRC – Dementia and Neurodegeneration Theme

Sponsors: Cambridge University Hospitals NHS Foundation Trust & University of Cambridge

Chief investigator

Professor Roger A Barker

Contact details

Clinical trial coordinator: Laura Oakley

[email protected]