COmBining memantine And cholinesterase inhibitors in Lewy body dementia Treatment trial
Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD)
Current interventions as of 21/04/2026: Memantine will be the Investigational Medicinal Product (IMP) for the COBALT trials. Memantine is currently licensed for the treatment of moderate to severe dementia in Alzheimer’s disease and is used off-licence in the UK for treatment of other dementias including DLB and PDD. IMP: Memantine 10mg tablets and Memantine 5mg tablets (Oral capsules). Placebo: Matched placebo tablets for memantine 5mg and 10 mg tablets will be manufactured and classed as an IMP for this trial (Oral capsules). All participants will receive an initial 4-week titration pack with clear instructions stated in the participant diary (part 1) dose instructions table. This table must be completed by the local trial team and the participant must be in receipt of the diary prior to starting the IMP. The 4-week titration schedule will start at 5mg daily in a single dose, taken in the morning. Thereafter, the dose will be increased by 5mg every week. The target dose will be 20mg/day, taken in the morning but titration will be based on tolerability and response. Potentially eligible patients will attend a screening visit during which consent will be obtained prior to any eligibility checks and the trial eligibility confirmation will be performed. This will include review of Liver and kidney function tests within the preceding 6 months. If no test results are available within this timeframe, a blood sample will be required to carry out these tests. A Mini Mental State Examination (MMSE) will be completed with the patient and a clinical diagnostic worksheet will be completed to confirm the patient’s diagnosis (Dementia with Lewy Bodies or Parkinson’s Disease Dementia). The patients will also be required to have a caregiver/informant in order to be eligible for the trial. The patient’s caregiver/informant should be a person that is in regular contact with the patient, who knows the patient well and is able to attend the trial follow-up visits as required. The
Current inclusion criteria as of 21/12/2023: 1. Patients with a diagnosis or clinical features consistent with established consensus criteria for probable DLB or probable PDD 2. Aged ≥55 years 3. MMSE score ≥8. Evidence of mild, moderate, or moderate to severe cognitive impairment on similar global cognitive scales previously completed by their clinical care team (e.g., Addenbrooke’s Cognitive Examination, Mini-Addenbrooke’s Cognitive Examination, Montreal Cognitive Assessment) can be used to pre-screen the patient, prior to approach. 4. Receiving a stable dose of AChEI for ≥12 weeks prior to baseline, with no expected plans for dose adjustment during the trial period; dose adjustment will be allowed during the trial, if clinically indicated, following discussion with PI and, if required, the central trial team 5. If receiving any antiparkinsonian treatment, antidepressants, anxiolytics, antipsychotics, or other drugs with significant psychotropic effects then dose must be stable for a minimum of 4 weeks prior to enrolment with no expected plans for dose adjustment during the trial period. Dose adjustment will be allowed during the trial if clinically indicated and will be documented. If a change in medication with psychotropic effects is required, this decision can be made by the treating clinician (e.g., starting an antidepressant in clinic) without consultation with the CI. In some instances, the clinician may feel it is appropriate/relevant to discuss this with the PI prior to prescribing, for example, if the clinician feels that the medication change may have an impact on the trial and/or trial medication. Any changes should however be documented in the patient’s concomitant medications electronic Case Report Form (eCRF). 6. Patients who lack capacity will be required to have a personal/professional nominated representative who is able to give informed consent on the patient’s behalf 7. Females must be postmenopausal and not receiving IVF treatment or must have
1. Atypical clinical features or course suggestive of an alternative dementia diagnosis. 2. Any clinically relevant concomitant disease that will affect ability to participate in the trial including, but not limited to, chronic renal disease stage 5, history of acute or chronic pancreatitis, epilepsy or former history of convulsions, patients with recent myocardial infarction (within last 6 months), uncompensated congestive heart failure (NYHA III-IV), or uncontrolled hypertension. 3. Patients with severe hepatic impairment based on known history and/or significant abnormalities identified in blood liver function tests (for example, levels in liver function tests that are 2-3 times higher than the upper limit of normal), which in the judgement of the local PI would exclude the patient from the trial.* 4. Patients taking memantine, amantadine, ketamine, or dextromethorphan. 5. Any neurological or major psychiatric diagnosis that may be contributing to cognitive impairment above and beyond that caused by the patients DLB or PDD. 6. Renally impaired patients with eGFR <35 mL/min/1.73m².† 7. Currently taking part in another clinical trial that would interfere with the outcomes of the COBALT trial. 8. If in the opinion of the investigator, the patient would be unable to comply with the trial procedures or has difficulty taking oral medications. 9. Patients without a reliable caregiver/informant. *LFTs should be repeated if they were not carried out at screening and were abnormal in the last 6 months and/or, in the judgement of the local PI, are clinically relevant to check before deciding trial entry. †U&Es should be repeated if they were not carried out at screening and were abnormal in the last 6 months and/or, in the judgement of the local PI, are clinically relevant to check before deciding trial entry. For example, a borderline eGRF <45 mL/min/1.73m².