Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This randomised, double-blinded, placebo-controlled study aims to establish metabolic improvements in subjects diagnosed with Alzheimer's Disease (AD) by treatment with CMA2 including N-acetyl-L-cysteine (NAC), L-carnitine-L-tartrate (LCAT), nicotinamide (niacinamide), and L-serine.
Participants will take the drug CMA2 or a placebo twice a day for 26 weeks. They will visit the clinic 4 times for checkups and tests.
This will be a randomised, double-blinded, placebo-controlled, multi-centre Phase 3 study with the aim to establish metabolic improvements in subjects diagnosed with AD by dietary supplementation with CMA2, including NAC, LCAT, niacinamide, and L-serine. The study will be performed at approximately 9 clinical sites in Turkey and aims to include a total of 676 evaluable subjects (up to 845 randomised).
The study comprises four clinical visits. Consenting subjects will be screened for eligibility (Visit 1; screening) according to study-specific eligibility criteria within 28 days prior to randomisation and start of IMP administration. Eligible subjects will be randomised on Day 1 (Visit 2) to 26 weeks of b.i.d. oral administration of either CMA2 or placebo (1:1). The first dose will be administered at the study clinic. The subjects will be observed for 2 hours post dose for the development of any allergic reactions or intolerance after taking the first dose. Subjects who cannot tolerate the study agents will be withdrawn from the study.
Visits at the study site will be performed at Week 13 (Visit 5) and Week 26 (Visit 8; end of treatment). Monthly telephone contacts will be scheduled with the patients. At the telephone visits IMP compliance, Concomitant medication and adverse event will be addressed.
The following clinical scales will be used to assess the effect of CMA2 on cognition and daily life activity: MMSE, ADAS-Cog, and ADCS-ADL. Blood samples will be collected for advanced plasma metabolomics, proteomics, and lipidomics analysis. Whole genome sequencing will not be performed.
Optional blood samples will be collected for p- tau217, Nfl, GFAP, and S-Urate analysis. Optional Saliva and faeces sampling for oral and gut microbiome will be collected. CSF samples will be optional collected for determination of Abeta42, total-Tau, p-Tau181 levels and Neurofilament light chain concentrations, and for advanced CSF metabolomics, proteomics, and lipidomics analysis. These samples will be decided by each investigator and will be analysed as exploratory endpoint.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Arm | Experimental |
| |
| Placebo Arm | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combined metabolic activators | Drug | A total of 20g of CMA2 with strawberry aroma and colouring agent will be given. The IMP will be provided as a soluble powder packed as individual dosages in identical sachets. The powder should be dissolved in 200 ml preferably cold water before use. The powder can also be used on yoghurt or other food. The subjects will take two daily oral doses of the IMP, one dose just after breakfast and one dose just after dinner. Subjects who cannot tolerate (e.g., diarrhoea) taking full dose will be withdrawn from the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score from baseline to end-of-treatment | The test administrator adds up points for the errors in each task for a total score ranging from 0 to 70. The greater the dysfunction, the greater the score. A score of 70 represents the most severe impairment and 0 represents the least impairment | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mini Mental State Examination (MMSE) score from baseline to end-of-treatment | MMSE is administered serially to assess the effect of time on the progression of dementia. The MMSE contains seven domains (including orientation, attention, recall) each with an assigned point value totaling 30. Severe cognitive impairment is indicated by a score of (≤9 points) moderate (10- 20 points) and mild (21-24 points). A score of 25 and over indicates normal cognition. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sevki SAHIN, Prof. Dr. | Contact | +90 216 606 33 00 | drsahin@gmail.com | |
| Ozlem Totuk, Dr. | Contact | +90 216 606 33 00 | totukozlem@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Sevki SAHIN, Prof. Dr. | Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences Istanbul 34766, Turkiye | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Neurology and Neuroscience, Faculty of Medicine, Alaaddin Keykubat University | Recruiting | Alanya | Turkey (Türkiye) |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Collagen and maltodextrin | Other | As placebo, a total of 20g of compound primarily containing collagen and maltodextrin will be administered. Placebo contains strawberry aroma flavouring and colouring agent. |
|
| Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) score from baseline to end-of-treatment | The 23 ADL items (Activities of Daily Living; 6 basic and 17 instrumental) assess the competence of patients with Alzheimer's Disease in activities of daily living. All responses should relate to the 4 weeks prior to the time of rating. The total score is 0-78, with low scores indicating more severe impairment. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| To evaluate compliance daily two doses treatment in patients | The subject will be instructed to bring all unused IMP and empty containers to the clinic visits on Week 13 and Week 26. | Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in body weight from baseline through-out the study | Body weight will be measured at Visit 1, Visit 5 and Visit 8 to evaluate the safety of metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in body height from baseline through-out the study | Body height will be measured at Visit 1, Visit 5 and Visit 8 to evaluate the safety of metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in BMI from baseline through-out the study | BMI will be assessed at Visit 1, Visit 5 and Visit 8 to evaluate the safety of metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in waist and hip circumference from baseline | Waist and hip circumference will be measured aat Visit 1, Visit 5 and Visit 8 to evaluate the safety of metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in blood pressure from baseline | Systolic and Diastolic Blood Pressure (mmHg) will be measured at Visit 1, Visit 5 and Visit 8 to evaluate the safety of metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in heart rate from baseline | Change in heart rate will be measured at Visit 1, Visit 5 and Visit 8 to evaluate the safety of metabolic cofactor supplementation | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in red blood cell count from baseline | Red Blood Cell count test will be performed to measure possible toxic effects of metabolic cofactor supplementation on the hematological system. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in platelet count from baseline | Platelet count test will be performed to measure possible toxic effects of metabolic cofactor supplementation on the hematological system. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in hemoglobin concentration from baseline | Hemoglobin concentrations will be assessed to measure possible toxic effects of the metabolic cofactor supplementation on hematological system. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in white blood cell count from baseline | White blood cell count test will be performed to measure possible toxic effects of the metabolic cofactor supplementation on hematological system. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Changes in kidney function tests from baseline | Kidney function tests (creatinine, urea, urate) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on kidney function. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Changes in kidney function tests from baseline | Kidney function tests (sodium, potassium) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on kidney function. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Changes in liver function tests [Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (ALP)] from baseline | Liver function tests (ALT, AST, GGT, ALP) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on liver function. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Changes in liver function tests (Total Bilirubin, and Albumin) from baseline | Liver function tests (Total Bilirubin, Albumin) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on liver function. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Changes in creatinine kinase (CK) level from baseline | Creatinine kinase (CK) level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Changes in blood lipid levels (total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C)) from baseline | Blood lipid levels (total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C)) will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Changes in blood glucose levels from baseline | Blood glucose levels will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in blood insulin level from baseline | Blood insulin level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Change in thyroid-stimulating hormone (TSH) level from baseline | Thyroid-stimulating hormone (TSH) level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation. | Visit 1, Visit 5 (13 weeks), Visit 8 (26 weeks) |
| Monitoring Adverse Events | This process aiming to monitoring of adverse events of metabolic cofactor supplementation. Adverse events, serious adverse events, serious adverse reactions, suspected unexpected serious adverse reactions will be monitored continuously and all events that occur at any time during the study will be reported in Case Report Forms. Any symptoms of intestinal discomfort or other side effects will be carefully recorded and all study subjects will be informed to contact (by phone or text message) the investigators immediately if they experience any symptoms of discomfort or any side effects during the intervention period | 26 weeks |
| Ataturk University, Faculty of Medicine, Department of Neurology, Erzurum, Turkey; Movement Disorders and Neuromodulation Center, Ataturk University | Recruiting | Erzurum | Turkey (Türkiye) |
|
| Behavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University | Recruiting | Istanbul | Turkey (Türkiye) |
|
| Haydarpaşa Numune Training and Research Hospital, University of Health Sciences Istanbul | Not yet recruiting | Istanbul | Turkey (Türkiye) |
|
| Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences Istanbul | Recruiting | Istanbul | Turkey (Türkiye) |
|
| SB Haseki Training and Research Hospital, Istanbul, University of Health Sciences Istanbul | Recruiting | Istanbul | Turkey (Türkiye) |
|
| Sultan Abdülhamid Han Training and Research Hospital, University of Health Sciences Istanbul | Recruiting | Istanbul | Turkey (Türkiye) |
|
| Umraniye Training and Research Hospital, University of Health Sciences Istanbul | Recruiting | Istanbul | Turkey (Türkiye) |
|
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D003094 | Collagen |
| C008315 | maltodextrin |
| ID | Term |
|---|---|
| D001704 | Biopolymers |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
| D016326 | Extracellular Matrix Proteins |
| D012596 | Scleroproteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided