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Trial record 4 of 5 for:    vitamin b3 | Alzheimer Disease

Metabolic Cofactor Supplementation in Alzheimer's Disease (AD) and Parkinson's Disease (PD) Patients

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ClinicalTrials.gov Identifier: NCT04044131
Recruitment Status : Recruiting
First Posted : August 5, 2019
Last Update Posted : February 13, 2020
Sponsor:
Collaborators:
ScandiBio Therapeutics AB
Alanya Alaaddin Keykubat University
Sahlgrenska University Hospital, Sweden
KTH Royal Institute of Technology
Information provided by (Responsible Party):
Prof. Lutfu Hanoglu, MD, Istanbul Medipol University Hospital

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Parkinson Disease Drug: Metabolic Cofactor Supplementation Drug: Sorbitol Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 1, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
Experimental: Treatment Arm
Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture.
Drug: Metabolic Cofactor Supplementation
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).

Placebo Comparator: Placebo Arm
Subjects will take a mixture of placebo as powder dissolved in water by mouth.
Drug: Sorbitol
As placebo, sorbitol (5g) flavoured with strawberry aroma and colouring agent will be given.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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).


Secondary Outcome Measures :
  1. Volumetric Magnetic resonance Imaging (MRI) and resting state functional magnetic resonance imaging (rest-fMRI) [ Time Frame: 12 weeks ]
    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.

  2. Neuropsychiatric Inventory (NPI) [ Time Frame: 4 weeks and 12 weeks ]
    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).

  3. Montreal Cognitive Assessment (MoCA) [ Time Frame: 4 weeks and 12 weeks ]
    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.

  4. Changes in serum omic profile from baseline [ Time Frame: 4 weeks and 12 weeks ]
    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.

  5. Microbiota analysis [ Time Frame: 4 weeks and 12 weeks ]
    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.

  6. Monitoring of adverse events [ Time Frame: 1 week, 4 weeks and 12 weeks ]
    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.

  7. Change in heart rate from baseline [ Time Frame: 1 week, 4 weeks and 12 weeks ]
    Heart rate will be measured at every visit to evaluate safety of metabolic cofactor supplementation.

  8. Change in blood pressure from baseline [ Time Frame: 1 week, 4 weeks and 12 weeks ]
    Blood pressure will be measured at every visit to evaluate safety of metabolic cofactor supplementation.

  9. Change in waist and hip circumference from baseline [ Time Frame: 1 week, 4 weeks and 12 weeks ]
    Waist and hip circumference will be measured at every visit to evaluate safety of metabolic cofactor supplementation.

  10. Change in body weight from baseline [ Time Frame: 1 week, 4 weeks and 12 weeks ]
    Body weight will be measured at every visit to evaluate safety of metabolic cofactor supplementation.

  11. Change of complete blood count from baseline [ Time Frame: 4 weeks and 12 weeks ]
    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.

  12. 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 ]
    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.

  13. 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 ]
    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.

  14. Changes in kidney function tests (creatinine, urea, urate, sodium, potassium) from baseline [ Time Frame: 4 weeks and 12 weeks ]
    Kidney function tests (creatinine, urea, urate, sodium, potassium) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on kidney function.

  15. Changes in creatinine kinase (CK) level from baseline [ Time Frame: 4 weeks and 12 weeks ]
    Creatinine kinase (CK) level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.

  16. Change in thyroid-stimulating hormone (TSH) level from baseline [ Time Frame: 4 weeks and 12 weeks ]
    Thyroid-stimulating hormone (TSH) level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.

  17. Change in blood insulin level from baseline [ Time Frame: 4 weeks and 12 weeks ]
    Blood insulin level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.

  18. Change in glycated haemoglobin (HbA1c) level from baseline [ Time Frame: 4 weeks and 12 weeks ]
    HbA1c level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.

  19. Changes in blood glucose levels from baseline [ Time Frame: 4 weeks and 12 weeks ]
    Blood glucose levels will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04044131


Contacts
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Contact: Lutfu Hanoglu, MD, PhD 0090 212 460 77 77 lhanoglu@medipol.edu.tr
Contact: Burak Yulug, MD, PhD 0090 242 513 48 41 burakyulug@gmail.com

Locations
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Turkey
Alanya Alaaddin Keykubat University Hospital Recruiting
Antalya, Turkey, 07400
Contact: Burak Yulug, MD, PhD    0090 242 513 48 41    burakyulug@gmail.com   
Principal Investigator: Burak Yulug, MD, PhD         
Medipol University Hospital Recruiting
Istanbul, Turkey, 34214
Contact: Lutfu Hanoglu, MD, PhD    0090 212 460 70 30    lhanoglu@medipol.edu.tr   
Principal Investigator: Lutfu Hanoglu, MD, PhD         
Sponsors and Collaborators
Istanbul Medipol University Hospital
ScandiBio Therapeutics AB
Alanya Alaaddin Keykubat University
Sahlgrenska University Hospital, Sweden
KTH Royal Institute of Technology
Investigators
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Principal Investigator: Lutfu Hanoglu, MD, PhD Medipol University
Principal Investigator: Burak Yulug, MD, PhD Alanya Alaaddin Keykubat University
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Responsible Party: Prof. Lutfu Hanoglu, MD, Professor, Istanbul Medipol University Hospital
ClinicalTrials.gov Identifier: NCT04044131    
Other Study ID Numbers: Metabolic Cofactor Study
First Posted: August 5, 2019    Key Record Dates
Last Update Posted: February 13, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Parkinson Disease
Alzheimer Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Synucleinopathies
Dementia
Tauopathies
Sorbitol
Cathartics
Gastrointestinal Agents