E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Alzheimer's disease is the most common type of dementia. Dementia is a condition which typically affects older people and impairs memory and thinking without affecting the level of consciousness |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Does the anti-epileptic medication Levetiracetam offer benefit to cognition in patients with AD who have not experienced an overt seizure |
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E.2.2 | Secondary objectives of the trial |
To determine if use of Levetiracetam is associated with significant side effects in patients with AD that have not experienced an overt seizure
To determine if use of Levetiracetam is associated with an effect on mood in patients with AD that have not experienced an overt seizure
To determine if use of Levetiracetam is associated with changes in quality of life in patients with AD that have not experienced an overt seizure or a change in the quality of life of their carers
To evaluate whether the electroencephalogram can be used as a surrogate marker to better predict which patients with AD may respond to treatment with Levetiracetam
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All participants: • Participant is willing and able to give informed consent for participation in the trial. • Participant has English as their first language
Participants with AD
• Male or Female, 50 years or above. • Diagnosed with mild to moderate AD (MMSE 10 to 26) • Meets the National Institute of Aging-Alzheimer's Association criteria for probable AD (2011) • Stable dose of current regular medication, including aceytlcholinesterase inhibitors if applicable, for at least 4 weeks prior to trial entry. • Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial and for 3 months thereafter. • Participant has clinically acceptable blood and urine test results (creatinine clearance >75 ml/minute; liver function tests <2x upper limit of normal) and ECG that does not demonstrate conduction block or significant ischaemia within three months of enrolment. • In the Investigator’s opinion, is able and willing to comply with all trial requirements. • Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial. • Reliable carer available
Carer of participant with AD • Male or Female aged 18 and above. • Principal carer for the participant with AD • Able to attend all home visit
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E.4 | Principal exclusion criteria |
The participant may not enter the trial if ANY of the following apply
Participants with AD • Pre-existing diagnosis of epilepsy • Clinical or laboratory evidence of a cause other than AD as a cause of their dementia • Laboratory evidence of significant renal impairment (creatinine clearance <75 ml/minute) or liver dysfunction (liver function tests >2x upper limit of normal) within the preceding three months • Visual or motor impairment that investigator deems severe enough to impair ability to complete computerised based touch screen task • Use of anti-epileptic medication including use for an indication other than epilepsy e.g. for pain or migraine within previous three months • Other severe neurological or medical condition. Examples include, significant stroke, heart failure, chronic renal failure, chronic liver failure within last 3 months • Major depression or other significant behavioural disturbance • Known allergy to Levetiracetam or history of previous adverse reaction to Levetiracetam Contraindications, warnings and special precautions to Levetiracetam use are not described further in the protocol and the investigator should refer to the Standard Product Characteristics • Female participant who is pregnant, lactating or planning pregnancy during the course of the trial. • Scheduled elective surgery or other procedures requiring general anaesthesia during the trial. • Participant with life expectancy of less than 6 months, or is inappropriate for placebo medication. • Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial.
Participants who have participated in another research trial involving an investigational medicinal product in the past 12 weeks will also be excluded
Carer of participant with AD • Carer has significant medical illness that will preclude adequate data capture during the study
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Outcome: Changes in cognition in patients while taking Levetiracetam as measured by computerised assessment of a hippocampal binding memory task |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Participants in the ILiAD Study will enter a crossover trial in which they will receive Levetiracetam for 12 weeks and Placebo for 12 weeks.
There will be assessments at baseline and at the start of the second phase of the trial (12 weeks). Assessments of efficacy will be made at 8 weeks (comparison to baseline) and at 20 weeks (comparison to 12 week assessment) |
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E.5.2 | Secondary end point(s) |
Secondary outcomes: 1. Determination whether Levetiracetam associates with significant side effects in patients with AD that have not experienced an overt seizure
2. To determine if use of Levetiracetam associates with an effect on mood in patients with AD that have not experienced an overt seizure
3. To determine if use of Levetiracetam associates with changes in quality of life in patients with AD that have not experienced an overt seizure or a change in the quality of life of their carers
4. To evaluate whether the electroencephalogram be used as a surrogate marker to better predict which patients with AD may respond to treatment with Levetiracetam
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Participants in the ILiAD Study will enter a crossover trial in which they will receive Levetiracetam for 12 weeks and Placebo for 12 weeks.
There will be assessments at baseline and at the start of the second phase of the trial (12 weeks).
End point assessments for secondary objectives 1 to 3 will be made at 8 weeks (comparison to baseline) and at 20 weeks (comparison to 12 week assessment)
Assessment of the EEG as a surrogate marker will compare baseline assessment of the EEG with cognitive outcomes at 8 and 20 weeks. Once the trial is unblinded, investigators will determine if there is a predictive value of EEG recording on response to Levetiracetam in study subjects |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 1 |