Alzheimer DiseasePhase 2NCT04044131
Metabolic Cofactor Supplementation in Alzheimer's Disease (AD) and Parkinson's Disease (PD) Patients
A Phase 2 study testing Metabolic Cofactor Supplementation and Sorbitol in people with Alzheimer Disease and Parkinson Disease, run by Istanbul Medipol University Hospital at 2 sites in Turkey (Türkiye).
Trial summary
This double-blind, randomized, placebo-controlled, investigator-initiated, multi-centre trial aims to establish metabolic improvements in AD and PD subjects by dietary supplementation with cofactors N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside and serine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alzheimer Disease, Parkinson Disease
- What is being tested?
- Metabolic Cofactor Supplementation and Sorbitol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesTurkey (Türkiye)
- Study dates
- 2 Dec 2019to 20 Apr 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women diagnosed with Parkinson's Disease (Hoehn Yahr 2-4, age >18 years) or men and women diagnosed with Alzheimer's Disease. Include patients older than 50 years with mild to moderate Alzheimer's disease according to ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale; ADAS≥12) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB; CDR≤2).
- Patients with stable treatments and clinical course
Who cannot join
- Inability or unwillingness to give written informed consent
- History of stroke, severe brain trauma, toxic drug exposure
- Neurological examination which indicate to Parkinson-Plus syndrome (i.e., pyramidal, cerebellar and autonomic dysfunction findings and gaze paralysis) for PD
- Uncontrolled Type 1 or type 2 diabetes
- Diarrhea (defined as more than 2 stool per day) within 7 days before enrolment
- Chronic kidney disease with an estimated glomerular filtration rate <60 ml/min/1.73m2
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- Significant cardiovascular co-morbidity (i.e. heart failure, documented coronary artery disease, valvular heart disease)
- Patients with active bronchial asthma
- Patients with phenylketonuria (contraindicated for NAC)
- Patients with histamine intolerance
- Clinically significant TSH level outside the normal range (0.04-6 mU/L)
- Known allergy for substances used in the study
- Concomitant medication use: Self-administration of dietary supplements such as any vitamins, omega-3 products, or plant stanol/sterol products within 1 month; Use of an antimicrobial agent in the 4 weeks preceding randomization
- Active smokers consuming >10 cigarettes/day
- Alcohol consumption over 192 grams for men and 128 grams for women per week
- Patients considered as inappropriate for this study for any reason (patients unable to undergo MRI study, noncompliance etc.)
- Active participation in another clinical study
Trial locations and contacts
2 sites in 1 country.
Turkey (Türkiye)2 sites
Alanya Alaaddin Keykubat University Hospital
Antalya, 07400
Medipol University Hospital
Istanbul, 34214
About this study
Official title: A Phase 2, Randomized, Placebo Controlled Study to Evaluate the Efficacy, Tolerability and Safety of Metabolic Cofactor Supplementation in Alzheimer's Disease (AD) And Parkinson's Disease (PD) Patients
This double-blind, randomized, placebo-controlled, investigator-initiated, multi-centre trial aims to establish metabolic improvements in AD and PD subjects by dietary supplementation with cofactors N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside and serine. Concomitant use of pivotal metabolic cofactors via simultaneous dietary supplementation will stimulate to enhance hepatic β-oxidation and this study's hypothesis is that this will result in increased mitochondrial activity in human brain cell-types.
Read the detailed description
In this study, investigators aim to activate mitochondria of brain cell-types in AD and PD patients by increasing the hepatic, plasma and brain levels of pivotal metabolic cofactors via simultaneous dietary supplementation of serine, L-carnitine, N-acetylcysteine (NAC) and nicotinamide riboside (NR).
The study is based on a three-step strategy to activate the mitochondria in human brain cells: (1) The investigators will use L-carnitine tartrate to enhance the transport of fatty acids across the mitochondrial membrane (by forming a long chain acetylcarnitine ester and being transported by carnitine palmitoyltransferase [CPT] I and CPT II) and to stabilize acetyl-CoA and coenzyme A levels. (2) Nicotinamide riboside, precursor of NAD+ will be included to boost the level of hepatic β-oxidation of fatty acids in mitochondria. Decreased electron transport chain function combined with impaired rates of fatty acid β-oxidation leads to the accumulation of incomplete products of β-oxidation, which combined with increased levels of reactive oxygen species (ROS), contribute to insulin resistance. Nicotinamide riboside stimulates the transfer of fatty acids from cytosol to mitochondria, similar to L-carnitine tartrate. (3) Two glutathione precursors, serine and N-acetylcysteine, will be included to increase glutathione levels in the hepatocytes. Increased glutathione levels will also protect against free radical-mediated oxidative stress generated by the increased β-oxidation of fatty acids in mitochondria.
Previous studies showed that each agent is able to activate mitochondria separately and a proof-of-concept study using serine supplementation, and a phase I study using this three-step approach resulted in a significant decrease in plasma metabolites associated with mitochondrial dysfunction without significant side effect. The novel design with this study is to give the L-carnitine, NR, serine and NAC as a cocktail. Based on investigators' earlier results, that this will improve the efficacy of the intervention.
The study population will consist of 60 Alzheimer's and 60 Parkinson's disease patients. Eligible subjects must have signed an informed consent, meet all inclusion criteria and have none of the exclusion criteria listed below. Patients will be randomized on a 2:1 basis to the cofactor mixture or placebo in two different centres.
The subjects will take a mixture of cofactors or matching placebo as powder dissolved in water by mouth. Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture. Half dosage of the co-factors will be given for two weeks (one dose taken just after dinner), and full dosage for 8 weeks (two equal doses taken just after breakfast and dinner). Patients who cannot tolerate taking full dose may continue the study with half dose (i.e. one dose taken just after dinner). Patients who cannot tolerate the study agents will be withdrawn from the study.
Active treatment duration will be 12 weeks for each subject and the total study duration is estimated as 6 months. Study comprises four clinical visits; (1) a screening visit, (2) randomization visit, (3) treatment visit and (4) end of treatment visit. At visit 1 and visit 4, all procedures including clinical and physical examination, adverse events recording, MRI volumetric and rest-state fMRI, determination of the motor, cognitive and behavioral functions using clinical scales, biochemical, omic and oral/gut microbiota analysis will be done. At visit 2, eligible study subjects will be randomized to active therapy or placebo groups and study agents will be dispensed. At visit 3, clinical and physical examination, determination of the motor, cognitive and behavioural functions using clinical scales, laboratory safety parameters, omic and oral/gut microbiota analysis will be repeated as in Visit 1. After the visit 4, participants will stop taking study agents.
A subject will be considered as having completed the study if he/she has completed all assessments at the End of Treatment Visit (Visit 4) and has been followed up until 12 weeks after initiation of the study drugs.
Statistics for the primary outcome parameter will be analysed by Mann-Whitney U test or t-test depending on the results of the normality test. For the secondary outcome parameters, one-way repeated measures ANOVA will be performed.
- Conditions
- Alzheimer Disease, Parkinson Disease
- Being tested
- Metabolic Cofactor Supplementation, Sorbitol
- Medical subject headings
- Alzheimer Disease, Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metabolic Cofactor SupplementationDrug
Dietary supplement consisting of serine, L-carnitine tartrate, N-acetylcysteine and nicotinamide riboside. Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture. Half dosage of the co-factors will be given for two weeks (one dose taken just after dinner), and full dosage for 8 weeks (two equal doses taken just after breakfast and dinner).
SorbitolDrug
As placebo, sorbitol (5g) flavoured with strawberry aroma and colouring agent will be given.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture. Receives: Drug: Metabolic Cofactor Supplementation |
| Placebo Arm | Placebo comparator | Subjects will take a mixture of placebo as powder dissolved in water by mouth. Receives: Drug: Sorbitol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mini Mental State Examination (MMSE)
The change in Mini Mental State Examination (MMSE) scores between the placebo and the treatment arms in AD patient from baseline to 4 weeks and 12 weeks. MMSE is global cognitive evaluation scale for AD patients. It consists of eleven questions and is evaluated over 30 points. It is normal between 24-30 points.
Measured: 4 weeks and 12 weeks
Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
The change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores between the placebo and the treatment arms in AD patients from baseline to 4 weeks and 12 weeks. ADAS-cog is cognitive evaluation scale for AD patients. ADAS-Cog includes 11 tasks that include both subject-completed tests and observer-based assessments. Together these tasks assess the cognitive domains of memory, language, and praxis. The ADAS-cog is scored between 0-70 and high scores indicate poor status.
Measured: 4 weeks and 12 weeks
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
The change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scores between the placebo and the treatment arms in AD patients from baseline to 4 weeks and 12 weeks. ADCS-ADL is daily life activity evaluation scale for AD patients. This is a questionnaire structured to evaluate functional capacity in AD patients. It is scored between 0-78 and low scores indicate addiction. It is applied to the patient's relatives.
Measured: 4 weeks and 12 weeks
Unified Parkinson's Disease Rating Scale (UPDRS)
The change in Unified Parkinson's Disease Rating Scale (UPDRS) scores between the placebo and the treatment arms in PD patients from baseline to 4 weeks and 12 weeks. UPDRS is motor evaluation scale for PD patients. The UPDRS is used to follow the longitudinal course of Parkinson's disease. UPDRS has four parts: Part I (non-motor experiences of daily living), Part II (motor experiences of daily living, Part III (motor examination) and Part IV (motor complications). The first part 4, the second part 13, the third part 14 and the fourth part consists of 11 items. Each item scored between 0 (none) and 4 (heaviest). A score of 147 on the UPDRS scale represents the worst (total disability) with a score of zero representing (no disability).
Measured: 4 weeks and 12 weeks
Secondary outcomes (19)
Volumetric Magnetic resonance Imaging (MRI) and resting state functional magnetic resonance imaging (rest-fMRI)
The change in central nervous system atrophy and resting state network activity between the placebo and the treatment arms in AD and PD patients from baseline to 12 weeks.
Measured: 12 weeks
Neuropsychiatric Inventory (NPI)
The change in Neuropsychiatric Inventory (NPI) scores between the placebo and the treatment arms in AD and PD patients from baseline to 4 weeks and 12 weeks. NPI is behavioural evaluation scale for PD and AD patients. It is evaluated delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, aberrant motor activity, night-time behavioral disturbances and appetite, eating abnormalities. It is applied to the patient's relatives. If the patient's relative verifies the presence of that symptom, it is continued with more specific questions of that area. Subsequently, multiplying the numerical values given for the frequency (1 rare-4 very frequent) and severity (1 mild-3 severe) of the symptom constitutes the score of that item. The maximum score can be 144. For each item, the distress caused by that symptom for the relative of the patient is also calculated over 6 points (0 none-5 very severe).
Measured: 4 weeks and 12 weeks
Montreal Cognitive Assessment (MoCA)
The change in Montreal Cognitive Assessment (MoCA) scores between the placebo and the treatment arms in PD patients from baseline to 4 weeks and 12 weeks. MoCA is global cognitive evaluation scale for PD patients. The MoCA evaluates different types of cognitive abilities. These include orientation, short-term memory/delayed recall, executive function/visuospatial ability, language abilities, abstraction, animal naming, attention, clock-drawing test. Scores on the MoCA range from zero to 30, with a score of 26 and higher generally considered normal.
Measured: 4 weeks and 12 weeks
Changes in serum omic profile from baseline
The change in omic profile between the placebo and the treatment arms in PD an AD patients from baseline to 4 weeks and 12 weeks. Neurodegenerative diseases are affected by a combination of genetic, epigenetic and environmental factors. Omic studies are useful for deciphering the molecular landscape of neurodegenerative diseases. Omic data collected from both the PD and AD patient group will be used to identify molecular networks, biomarkers, and possible therapeutic targets through system biology. The aim of this study is to determine possible subtypes of disease based on the patients' response to treatment and to translate the network-based findings into clinically applicable tools for personalized medical practice. Serum omic analysis will include generation of untargeted omics data in Sweden. Biomarkers will be analysed by proximity extension and proximity ligation technologies (PEA and PLA) providing assays with high specificity and sensitivity in complex biological matrices.
Measured: 4 weeks and 12 weeks
Microbiota analysis
The change in gut microbiota between the placebo and the treatment arms in PD an AD patients from baseline to 4 weeks and 12 weeks. Faeces and saliva samples will be collected to assess changes in gut microbiota. Instructions on specimen collection will be given during the first visit. Microbiota will be assessed using shot-gun metagenomic techniques.
Measured: 4 weeks and 12 weeks
Monitoring of adverse events
This process aiming to monitoring of adverse events of metabolic cofactor supplementation. Adverse events and serious adverse events will be monitored continuously and all adverse 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.
Measured: 1 week, 4 weeks and 12 weeks
Change in heart rate from baseline
Heart rate will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Measured: 1 week, 4 weeks and 12 weeks
Change in blood pressure from baseline
Blood pressure will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Measured: 1 week, 4 weeks and 12 weeks
Change in waist and hip circumference from baseline
Waist and hip circumference will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Measured: 1 week, 4 weeks and 12 weeks
Change in body weight from baseline
Body weight will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Measured: 1 week, 4 weeks and 12 weeks
Change of complete blood count from baseline
Complete blood count includes number of blood cells and concentration of hemoglobin. Complete blood count will be performed to measure possible toxic effects of the metabolic cofactor supplementation on hematological system.
Measured: 4 weeks and 12 weeks
Changes in liver function tests (alkaline phosphatase (ALP), alanine aminotransferase (ALT), Aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total and direct Bilirubin, Albumin) from baseline
Liver function tests (AST, ALT, GGT, total and direct Bilirubin, Albumin) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on liver function.
Measured: 4 weeks and 12 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.
Measured: 4 weeks and 12 weeks
Changes in kidney function tests (creatinine, urea, urate, sodium, potassium) from baseline
Kidney function tests (creatinine, urea, urate, sodium, potassium) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on kidney function.
Measured: 4 weeks and 12 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.
Measured: 4 weeks and 12 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.
Measured: 4 weeks and 12 weeks
Change in blood insulin level from baseline
Blood insulin level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Measured: 4 weeks and 12 weeks
Change in glycated haemoglobin (HbA1c) level from baseline
HbA1c level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Measured: 4 weeks and 12 weeks
Changes in blood glucose levels from baseline
Blood glucose levels will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Measured: 4 weeks and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2019
- Study start2 Dec 2019
- Primary completion15 Mar 2021
- Study completion20 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A total of 60 Alzheimer's and 60 Parkinson's disease patients will be randomized on a 2:1 basis to the cofactor mixture or placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istanbul Medipol University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- ScandiBio Therapeutics AB, Alanya Alaaddin Keykubat University, Sahlgrenska University Hospital, KTH Royal Institute of Technology
- Responsible party
- Principal investigator, Prof. Lutfu Hanoglu, MD, Istanbul Medipol University Hospital
- Investigators
- Lutfu Hanoglu, MD, PhD, Principal investigator, Medipol UniversityBurak Yulug, MD, PhD, Principal investigator, Alanya Alaaddin Keykubat University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04044131
- Sponsor's protocol ID
- Metabolic Cofactor Study
- Status last verified
- Aug 2022
- First submitted
- 17 Jul 2019
- Last updated
- 8 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Yulug B, Altay O, Li X, Hanoglu L, Cankaya S, Velioglu HA, Lam S, Yang H, Coskun E, Idil E, Bayraktaroglu Z, Nogaylar R, Ozsimsek A, Yildirim S, Bolat I, Kiliclioglu M, Bayram C, Yuksel N, Tozlu OO, Arif M, Shoaie S, Hacimuftuoglu A, Zhang C, Nielsen J, Turkez H, Boren J, Uhlen M, Mardinoglu A. Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial. Brain Commun. 2025 Jan 6;7(1):fcae478. doi: 10.1093/braincomms/fcae478. eCollection 2025.
PubMed 39816194Yulug B, Altay O, Li X, Hanoglu L, Cankaya S, Lam S, Velioglu HA, Yang H, Coskun E, Idil E, Nogaylar R, Ozsimsek A, Bayram C, Bolat I, Oner S, Tozlu OO, Arslan ME, Hacimuftuoglu A, Yildirim S, Arif M, Shoaie S, Zhang C, Nielsen J, Turkez H, Boren J, Uhlen M, Mardinoglu A. Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial. Transl Neurodegener. 2023 Jan 26;12(1):4. doi: 10.1186/s40035-023-00336-2.
PubMed 36703196
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Placebo Controlled Study to Evaluate the Efficacy, Tolerability and Safety of Metabolic Cofactor Supplementation in Alzheimer's Disease (AD) And Parkinson's Disease (PD) Patients
- ClinicalTrials.gov ID
- NCT04044131
- Acronym / sponsor ID
- Metabolic Cofactor Study
- Conditions
- Alzheimer Disease, Parkinson Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Istanbul Medipol University HospitalUniversity, hospital or other
- Collaborators
- ScandiBio Therapeutics AB, Alanya Alaaddin Keykubat University, Sahlgrenska University Hospital, KTH Royal Institute of Technology
- Study start
- 2 Dec 2019 (actual)
- Primary completion
- 15 Mar 2021 (actual)
- Study completion
- 20 Apr 2021 (actual)
- First posted
- 5 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This double-blind, randomized, placebo-controlled, investigator-initiated, multi-centre trial aims to establish metabolic improvements in AD and PD subjects by dietary supplementation with cofactors N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside and serine. Concomitant use of pivotal metabolic cofactors via simultaneous dietary supplementation will stimulate to enhance hepatic β-oxidation and this study's hypothesis is that this will result in increased mitochondrial activity in human brain cell-types.
Detailed description
In this study, investigators aim to activate mitochondria of brain cell-types in AD and PD patients by increasing the hepatic, plasma and brain levels of pivotal metabolic cofactors via simultaneous dietary supplementation of serine, L-carnitine, N-acetylcysteine (NAC) and nicotinamide riboside (NR).
The study is based on a three-step strategy to activate the mitochondria in human brain cells: (1) The investigators will use L-carnitine tartrate to enhance the transport of fatty acids across the mitochondrial membrane (by forming a long chain acetylcarnitine ester and being transported by carnitine palmitoyltransferase [CPT] I and CPT II) and to stabilize acetyl-CoA and coenzyme A levels. (2) Nicotinamide riboside, precursor of NAD+ will be included to boost the level of hepatic β-oxidation of fatty acids in mitochondria. Decreased electron transport chain function combined with impaired rates of fatty acid β-oxidation leads to the accumulation of incomplete products of β-oxidation, which combined with increased levels of reactive oxygen species (ROS), contribute to insulin resistance. Nicotinamide riboside stimulates the transfer of fatty acids from cytosol to mitochondria, similar to L-carnitine tartrate. (3) Two glutathione precursors, serine and N-acetylcysteine, will be included to increase glutathione levels in the hepatocytes. Increased glutathione levels will also protect against free radical-mediated oxidative stress generated by the increased β-oxidation of fatty acids in mitochondria.
Previous studies showed that each agent is able to activate mitochondria separately and a proof-of-concept study using serine supplementation, and a phase I study using this three-step approach resulted in a significant decrease in plasma metabolites associated with mitochondrial dysfunction without significant side effect. The novel design with this study is to give the L-carnitine, NR, serine and NAC as a cocktail. Based on investigators' earlier results, that this will improve the efficacy of the intervention.
The study population will consist of 60 Alzheimer's and 60 Parkinson's disease patients. Eligible subjects must have signed an informed consent, meet all inclusion criteria and have none of the exclusion criteria listed below. Patients will be randomized on a 2:1 basis to the cofactor mixture or placebo in two different centres.
The subjects will take a mixture of cofactors or matching placebo as powder dissolved in water by mouth. Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture. Half dosage of the co-factors will be given for two weeks (one dose taken just after dinner), and full dosage for 8 weeks (two equal doses taken just after breakfast and dinner). Patients who cannot tolerate taking full dose may continue the study with half dose (i.e. one dose taken just after dinner). Patients who cannot tolerate the study agents will be withdrawn from the study.
Active treatment duration will be 12 weeks for each subject and the total study duration is estimated as 6 months. Study comprises four clinical visits; (1) a screening visit, (2) randomization visit, (3) treatment visit and (4) end of treatment visit. At visit 1 and visit 4, all procedures including clinical and physical examination, adverse events recording, MRI volumetric and rest-state fMRI, determination of the motor, cognitive and behavioral functions using clinical scales, biochemical, omic and oral/gut microbiota analysis will be done. At visit 2, eligible study subjects will be randomized to active therapy or placebo groups and study agents will be dispensed. At visit 3, clinical and physical examination, determination of the motor, cognitive and behavioural functions using clinical scales, laboratory safety parameters, omic and oral/gut microbiota analysis will be repeated as in Visit 1. After the visit 4, participants will stop taking study agents.
A subject will be considered as having completed the study if he/she has completed all assessments at the End of Treatment Visit (Visit 4) and has been followed up until 12 weeks after initiation of the study drugs.
Statistics for the primary outcome parameter will be analysed by Mann-Whitney U test or t-test depending on the results of the normality test. For the secondary outcome parameters, one-way repeated measures ANOVA will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A total of 60 Alzheimer's and 60 Parkinson's disease patients will be randomized on a 2:1 basis to the cofactor mixture or placebo.
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Metabolic Cofactor SupplementationSubjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture. |
| Placebo Arm | Placebo comparator | Drug: SorbitolSubjects will take a mixture of placebo as powder dissolved in water by mouth. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Men and women diagnosed with Parkinson's Disease (Hoehn Yahr 2-4, age >18 years) or men and women diagnosed with Alzheimer's Disease. Include patients older than 50 years with mild to moderate Alzheimer's disease according to ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale; ADAS≥12) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB; CDR≤2).
- Patients with stable treatments and clinical course
Key exclusion criteria (17 listed)
- Inability or unwillingness to give written informed consent
- History of stroke, severe brain trauma, toxic drug exposure
- Neurological examination which indicate to Parkinson-Plus syndrome (i.e., pyramidal, cerebellar and autonomic dysfunction findings and gaze paralysis) for PD
- Uncontrolled Type 1 or type 2 diabetes
- Diarrhea (defined as more than 2 stool per day) within 7 days before enrolment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metabolic Cofactor SupplementationDietary supplement consisting of serine, L-carnitine tartrate, N-acetylcysteine and nicotinamide riboside. Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture. Half dosage of the co-factors will be given for two weeks (one dose taken just after dinner), and full dosage for 8 weeks (two equal doses taken just after breakfast and dinner). | Drug | Treatment Arm |
| SorbitolAs placebo, sorbitol (5g) flavoured with strawberry aroma and colouring agent will be given. | Drug | Placebo Arm |
Primary outcome
Mini Mental State Examination (MMSE)
Time frame: 4 weeks and 12 weeks
The change in Mini Mental State Examination (MMSE) scores between the placebo and the treatment arms in AD patient from baseline to 4 weeks and 12 weeks. MMSE is global cognitive evaluation scale for AD patients. It consists of eleven questions and is evaluated over 30 points. It is normal between 24-30 points.
Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
Time frame: 4 weeks and 12 weeks
The change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores between the placebo and the treatment arms in AD patients from baseline to 4 weeks and 12 weeks. ADAS-cog is cognitive evaluation scale for AD patients. ADAS-Cog includes 11 tasks that include both subject-completed tests and observer-based assessments. Together these tasks assess the cognitive domains of memory, language, and praxis. The ADAS-cog is scored between 0-70 and high scores indicate poor status.
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Time frame: 4 weeks and 12 weeks
The change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scores between the placebo and the treatment arms in AD patients from baseline to 4 weeks and 12 weeks. ADCS-ADL is daily life activity evaluation scale for AD patients. This is a questionnaire structured to evaluate functional capacity in AD patients. It is scored between 0-78 and low scores indicate addiction. It is applied to the patient's relatives.
Unified Parkinson's Disease Rating Scale (UPDRS)
Time frame: 4 weeks and 12 weeks
The change in Unified Parkinson's Disease Rating Scale (UPDRS) scores between the placebo and the treatment arms in PD patients from baseline to 4 weeks and 12 weeks. UPDRS is motor evaluation scale for PD patients. The UPDRS is used to follow the longitudinal course of Parkinson's disease. UPDRS has four parts: Part I (non-motor experiences of daily living), Part II (motor experiences of daily living, Part III (motor examination) and Part IV (motor complications). The first part 4, the second part 13, the third part 14 and the fourth part consists of 11 items. Each item scored between 0 (none) and 4 (heaviest). A score of 147 on the UPDRS scale represents the worst (total disability) with a score of zero representing (no disability).
19 secondary outcomes
Volumetric Magnetic resonance Imaging (MRI) and resting state functional magnetic resonance imaging (rest-fMRI)
Time frame: 12 weeks
Neuropsychiatric Inventory (NPI)
Time frame: 4 weeks and 12 weeks
Montreal Cognitive Assessment (MoCA)
Time frame: 4 weeks and 12 weeks
Changes in serum omic profile from baseline
Time frame: 4 weeks and 12 weeks
Microbiota analysis
Time frame: 4 weeks and 12 weeks
Monitoring of adverse events
Time frame: 1 week, 4 weeks and 12 weeks
Change in heart rate from baseline
Time frame: 1 week, 4 weeks and 12 weeks
Change in blood pressure from baseline
Time frame: 1 week, 4 weeks and 12 weeks
Change in waist and hip circumference from baseline
Time frame: 1 week, 4 weeks and 12 weeks
Change in body weight from baseline
Time frame: 1 week, 4 weeks and 12 weeks
Change of complete blood count from baseline
Time frame: 4 weeks and 12 weeks
Changes in liver function tests (alkaline phosphatase (ALP), alanine aminotransferase (ALT), Aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total and direct Bilirubin, Albumin) from baseline
Time frame: 4 weeks and 12 weeks
Changes in blood lipid levels (total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C)) from baseline
Time frame: 4 weeks and 12 weeks
Changes in kidney function tests (creatinine, urea, urate, sodium, potassium) from baseline
Time frame: 4 weeks and 12 weeks
Changes in creatinine kinase (CK) level from baseline
Time frame: 4 weeks and 12 weeks
Change in thyroid-stimulating hormone (TSH) level from baseline
Time frame: 4 weeks and 12 weeks
Change in blood insulin level from baseline
Time frame: 4 weeks and 12 weeks
Change in glycated haemoglobin (HbA1c) level from baseline
Time frame: 4 weeks and 12 weeks
Changes in blood glucose levels from baseline
Time frame: 4 weeks and 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2022.
- Derived from this study: PubMed 39816194Yulug B, Altay O, Li X, Hanoglu L, Cankaya S, Velioglu HA, Lam S, Yang H, Coskun E, Idil E, Bayraktaroglu Z, Nogaylar R, Ozsimsek A, Yildirim S, Bolat I, Kiliclioglu M, Bayram C, Yuksel N, Tozlu OO, Arif M, Shoaie S, Hacimuftuoglu A, Zhang C, Nielsen J, Turkez H, Boren J, Uhlen M, Mardinoglu A. Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial. Brain Commun. 2025 Jan 6;7(1):fcae478. doi: 10.1093/braincomms/fcae478. eCollection 2025.
- Derived from this study: PubMed 36703196Yulug B, Altay O, Li X, Hanoglu L, Cankaya S, Lam S, Velioglu HA, Yang H, Coskun E, Idil E, Nogaylar R, Ozsimsek A, Bayram C, Bolat I, Oner S, Tozlu OO, Arslan ME, Hacimuftuoglu A, Yildirim S, Arif M, Shoaie S, Zhang C, Nielsen J, Turkez H, Boren J, Uhlen M, Mardinoglu A. Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial. Transl Neurodegener. 2023 Jan 26;12(1):4. doi: 10.1186/s40035-023-00336-2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lutfu Hanoglu, MD, PhD principal investigator
Medipol University
Burak Yulug, MD, PhD principal investigator
Alanya Alaaddin Keykubat University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metabolic Cofactor Supplementation and Sorbitol in people with Alzheimer Disease and Parkinson Disease, run by Istanbul Medipol University Hospital at 2 sites in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mini Mental State Examination (MMSE) (time frame: 4 weeks and 12 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04044131, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2022.