NET-PD LS-1 Creatine in Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT00449865

Recruitment Status : Terminated (Futility)

First Posted : March 21, 2007

Results First Posted : April 2, 2015

Last Update Posted : April 2, 2015

Sponsor:

Collaborator:

National Institute of Neurological Disorders and Stroke (NINDS)

Information provided by (Responsible Party):

Karl Kieburtz, University of Rochester

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Parkinson's Disease
Interventions	Drug: creatine Other: placebo
Enrollment	1741

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Placebo	Creatine
Arm/Group Description	placebo: an inactive substance	creatine monohydrate (10 gram /day)
Arm/Group Description	placebo: an inactive substance	creatine monohydrate (10 gram /day)
Period Title: Overall Study
Started	867	874
Completed Year 1	802 ^[1]	822 ^[2]
Completed Year 2	768 ^[3]	766 ^[4]
Completed Year 3	719 ^[5]	715 ^[6]
Completed Year 4	521 ^[7]	523 ^[8]
Completed	345 ^[9]	340 ^[10]
Not Completed	522	534
Reason Not Completed
Withdrawal by Subject	110	110
Lost to Follow-up	36	37
Physician Decision	13	12
Death	31	40
Protocol Violation	8	7
Study was stopped	324	328
[1] 867 Expected at Year 1 [2] 874 Expected at Year 1 [3] 867 Expected at Year 2 [4] 874 Expected at Year 2 [5] 867 Expected at Year 3 [6] 874 Expected at Year 3 [7] 679 Expected at Year 4 [8] 686 Expected at Year 4 [9] 478 Expected at Year 5 [10] 477 Expected at Year 5

Baseline Characteristics

Arm/Group Title		Placebo	Creatine	Total
Arm/Group Description		placebo: an inactive substance	creatine 5 grams twice daily	Total of all reporting groups
Arm/Group Description		placebo: an inactive substance	creatine 5 grams twice daily	Total of all reporting groups
Overall Number of Baseline Participants		867	874	1741
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	867 participants	874 participants	1741 participants
		61.5 (9.6)	62.1 (9.7)	61.8 (9.6)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	867 participants	874 participants	1741 participants
	Female	313 36.1%	305 34.9%	618 35.5%
	Male	554 63.9%	569 65.1%	1123 64.5%
Time since diagnosis, y Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	867 participants	874 participants	1741 participants
		1.6 (1.1)	1.5 (1.1)	1.5 (1.1)
Total Unified Parkinson's Disease Rating Scale (UPDRS) ^[1] Mean (Standard Deviation) Unit of measure: Units on a scale
	Number Analyzed	867 participants	874 participants	1741 participants
		25.9 (11)	26.5 (11.7)	26.2 (11.4)
		[1] Measure Description: The total UPDRS is the sum of parts I, II, and III. The possible range of the total UPDRS is from 0-176. Higher values indicate worse outcomes.

Outcome Measures

1.Primary Outcome


Title	The Global Outcome Combined Information on Change From Baseline in Schwab England Activities of Daily Living, 39-Item Parkinson's Disease Questionnaire, Ambulatory Capacity, Symbol Digit Modalities, and Modified Rankin at 5 Years.
Description	All outcomes were coded such that higher scores indicated worse outcom...
Description	All outcomes were coded such that higher scores indicated worse outcomes. Patients were ranked on each outcome and their ranks were summed (summed-ranks). Higher summed ranks (range, 5-4775) indicate worse outcomes. The mean summed ranks were compared by treatment group by a global statistical test (GST).
Time Frame	Change from baseline to 5 YEARS

Outcome Measure Data

Analysis Population Description

Intent-to-Treat sample: n = 955, participants randomized at least 5 years before July 2013 (time of planned interim analysis).


Arm/Group Title	Placebo	Creatine
Arm/Group Description:	placebo: an inactive substance	creatine monohydrate (10 grams/day)
Arm/Group Description:	placebo: an inactive substance	creatine monohydrate (10 grams/day)
Overall Number of Participants Analyzed	478	477
Mean (95% Confidence Interval) Unit of Measure: summed-ranks
	2360 (2249 to 2470)	2414 (2304 to 2524)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Creatine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.45
	Comments	[Not Specified]
	Method	Global Statistical Test
	Comments	The global statistical test yielded t = -0.75 (2-sided p-value = .45, df=1865.8).

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Placebo	Creatine
Arm/Group Description	placebo: an inactive substance	creatine 5 grams twice daily
Arm/Group Description	placebo: an inactive substance	creatine 5 grams twice daily
All-Cause Mortality
	Placebo	Creatine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Placebo	Creatine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	347/867 (40.02%)	315/874 (36.04%)
Blood and lymphatic system disorders
Anaemia	0/867 (0.00%)	1/874 (0.11%)
Haemolytic anaemia	1/867 (0.12%)	0/874 (0.00%)
Cardiac disorders
Angina pectoris	1/867 (0.12%)	2/874 (0.23%)
Angina unstable	1/867 (0.12%)	1/874 (0.11%)
Aortic valve disease	1/867 (0.12%)	0/874 (0.00%)
Aortic valve incompetence	1/867 (0.12%)	0/874 (0.00%)
Atrial fibrillation	4/867 (0.46%)	9/874 (1.03%)
Bradycardia	4/867 (0.46%)	0/874 (0.00%)
Brugada syndrome	0/867 (0.00%)	1/874 (0.11%)
Cardiac arrest	4/867 (0.46%)	7/874 (0.80%)
Cardiac disorder	1/867 (0.12%)	0/874 (0.00%)
Cardiac failure	1/867 (0.12%)	0/874 (0.00%)
Cardiac failure congestive	1/867 (0.12%)	3/874 (0.34%)
Cardio-respiratory arrest	1/867 (0.12%)	3/874 (0.34%)
Cardiopulmonary failure	1/867 (0.12%)	0/874 (0.00%)
Coronary artery disease	3/867 (0.35%)	4/874 (0.46%)
Coronary artery occlusion	1/867 (0.12%)	0/874 (0.00%)
Coronary artery stenosis	1/867 (0.12%)	1/874 (0.11%)
Diastolic dysfunction	1/867 (0.12%)	0/874 (0.00%)
Hypertensive heart disease	1/867 (0.12%)	0/874 (0.00%)
Mitral valve stenosis	0/867 (0.00%)	1/874 (0.11%)
Myocardial infarction	8/867 (0.92%)	12/874 (1.37%)
Myocardial ischaemia	0/867 (0.00%)	2/874 (0.23%)
Palpitations	1/867 (0.12%)	0/874 (0.00%)
Sick sinus syndrome	0/867 (0.00%)	1/874 (0.11%)
Ventricular fibrillation	1/867 (0.12%)	0/874 (0.00%)
Ventricular tachycardia	0/867 (0.00%)	1/874 (0.11%)
Congenital, familial and genetic disorders
Congenital coronary artery malformation	1/867 (0.12%)	0/874 (0.00%)
Factor V deficiency	0/867 (0.00%)	1/874 (0.11%)
Ear and labyrinth disorders
Vertigo	4/867 (0.46%)	1/874 (0.11%)
Vertigo positional	0/867 (0.00%)	1/874 (0.11%)
Endocrine disorders
Goitre	2/867 (0.23%)	0/874 (0.00%)
Hyperparathyroidism	1/867 (0.12%)	0/874 (0.00%)
Eye disorders
Amaurosis fugax	0/867 (0.00%)	1/874 (0.11%)
Blindness transient	0/867 (0.00%)	1/874 (0.11%)
Macular oedema	1/867 (0.12%)	0/874 (0.00%)
Gastrointestinal disorders
Abdominal adhesions	1/867 (0.12%)	0/874 (0.00%)
Abdominal hernia	0/867 (0.00%)	2/874 (0.23%)
Abdominal pain	2/867 (0.23%)	2/874 (0.23%)
Abdominal pain upper	1/867 (0.12%)	0/874 (0.00%)
Anal fissure	0/867 (0.00%)	1/874 (0.11%)
Ascites	0/867 (0.00%)	1/874 (0.11%)
Colitis	0/867 (0.00%)	1/874 (0.11%)
Colitis ischaemic	0/867 (0.00%)	3/874 (0.34%)
Constipation	1/867 (0.12%)	1/874 (0.11%)
Diarrhoea	2/867 (0.23%)	1/874 (0.11%)
Dyspepsia	1/867 (0.12%)	0/874 (0.00%)
Dysphagia	1/867 (0.12%)	0/874 (0.00%)
Faecaloma	1/867 (0.12%)	0/874 (0.00%)
Gastrointestinal haemorrhage	2/867 (0.23%)	1/874 (0.11%)
Hiatus hernia	0/867 (0.00%)	1/874 (0.11%)
Ileus	1/867 (0.12%)	2/874 (0.23%)
Impaired gastric emptying	0/867 (0.00%)	1/874 (0.11%)
Inguinal hernia	1/867 (0.12%)	1/874 (0.11%)
Intestinal obstruction	3/867 (0.35%)	6/874 (0.69%)
Nausea	2/867 (0.23%)	0/874 (0.00%)
Oesophageal achalasia	0/867 (0.00%)	2/874 (0.23%)
Oesophageal stenosis	0/867 (0.00%)	1/874 (0.11%)
Oesophageal ulcer haemorrhage	0/867 (0.00%)	1/874 (0.11%)
Pharyngoesophageal diverticulum	0/867 (0.00%)	1/874 (0.11%)
Rectal haemorrhage	0/867 (0.00%)	1/874 (0.11%)
Small intestinal obstruction	2/867 (0.23%)	3/874 (0.34%)
Upper gastrointestinal haemorrhage	1/867 (0.12%)	2/874 (0.23%)
Vomiting	3/867 (0.35%)	0/874 (0.00%)
General disorders
Adverse drug reaction	0/867 (0.00%)	1/874 (0.11%)
Asthenia	5/867 (0.58%)	2/874 (0.23%)
Chest discomfort	2/867 (0.23%)	0/874 (0.00%)
Chest pain	15/867 (1.73%)	14/874 (1.60%)
Cyst	0/867 (0.00%)	2/874 (0.23%)
Death	2/867 (0.23%)	5/874 (0.57%)
Drug interaction	1/867 (0.12%)	0/874 (0.00%)
Facial pain	0/867 (0.00%)	1/874 (0.11%)
Fatigue	0/867 (0.00%)	1/874 (0.11%)
Gait disturbance	1/867 (0.12%)	0/874 (0.00%)
Medical device complication	1/867 (0.12%)	0/874 (0.00%)
Non-cardiac chest pain	2/867 (0.23%)	2/874 (0.23%)
Pain	9/867 (1.04%)	4/874 (0.46%)
Ulcer	2/867 (0.23%)	1/874 (0.11%)
Hepatobiliary disorders
Bile duct stone	0/867 (0.00%)	1/874 (0.11%)
Cholangitis	0/867 (0.00%)	1/874 (0.11%)
Cholecystitis	2/867 (0.23%)	3/874 (0.34%)
Cholelithiasis	0/867 (0.00%)	3/874 (0.34%)
Gallbladder disorder	1/867 (0.12%)	0/874 (0.00%)
Immune system disorders
Drug hypersensitivity	1/867 (0.12%)	1/874 (0.11%)
Infections and infestations
Abscess	0/867 (0.00%)	1/874 (0.11%)
Appendicitis	4/867 (0.46%)	1/874 (0.11%)
Appendicitis perforated	0/867 (0.00%)	1/874 (0.11%)
Bacterial infection	1/867 (0.12%)	0/874 (0.00%)
Bronchitis	1/867 (0.12%)	1/874 (0.11%)
Cellulitis	4/867 (0.46%)	4/874 (0.46%)
Clostridial infection	1/867 (0.12%)	1/874 (0.11%)
Clostridium difficile colitis	0/867 (0.00%)	1/874 (0.11%)
Coccidioidomycosis	1/867 (0.12%)	0/874 (0.00%)
Creutzfeldt-Jakob disease	1/867 (0.12%)	0/874 (0.00%)
Cystitis	1/867 (0.12%)	1/874 (0.11%)
Cytomegalovirus infection	0/867 (0.00%)	1/874 (0.11%)
Diverticulitis	2/867 (0.23%)	3/874 (0.34%)
Gastroenteritis	2/867 (0.23%)	0/874 (0.00%)
Groin abscess	0/867 (0.00%)	1/874 (0.11%)
Herpes zoster	1/867 (0.12%)	0/874 (0.00%)
Hip infection	1/867 (0.12%)	0/874 (0.00%)
Infection	1/867 (0.12%)	4/874 (0.46%)
Influenza	1/867 (0.12%)	1/874 (0.11%)
Intervertebral discitis	1/867 (0.12%)	0/874 (0.00%)
Kidney infection	1/867 (0.12%)	1/874 (0.11%)
Labyrinthitis	1/867 (0.12%)	0/874 (0.00%)
Liver abscess	1/867 (0.12%)	0/874 (0.00%)
Lung infection	0/867 (0.00%)	1/874 (0.11%)
Meningitis bacterial	1/867 (0.12%)	0/874 (0.00%)
Meningitis viral	1/867 (0.12%)	0/874 (0.00%)
Oesophageal infection	1/867 (0.12%)	0/874 (0.00%)
Osteomyelitis	1/867 (0.12%)	0/874 (0.00%)
Peridiverticulitis	0/867 (0.00%)	1/874 (0.11%)
Pharyngitis	1/867 (0.12%)	0/874 (0.00%)
Pneumonia	18/867 (2.08%)	16/874 (1.83%)
Pyelonephritis	1/867 (0.12%)	1/874 (0.11%)
Sepsis	1/867 (0.12%)	1/874 (0.11%)
Septic shock	1/867 (0.12%)	0/874 (0.00%)
Sinusitis	1/867 (0.12%)	0/874 (0.00%)
Staphylococcal infection	2/867 (0.23%)	0/874 (0.00%)
Urinary tract infection	9/867 (1.04%)	5/874 (0.57%)
Urosepsis	4/867 (0.46%)	0/874 (0.00%)
Injury, poisoning and procedural complications
Accidental overdose	1/867 (0.12%)	1/874 (0.11%)
Arterial injury	0/867 (0.00%)	1/874 (0.11%)
Avulsion fracture	0/867 (0.00%)	1/874 (0.11%)
Cervical vertebral fracture	1/867 (0.12%)	0/874 (0.00%)
Clavicle fracture	0/867 (0.00%)	1/874 (0.11%)
Concussion	1/867 (0.12%)	1/874 (0.11%)
Contusion	2/867 (0.23%)	0/874 (0.00%)
Fall	11/867 (1.27%)	7/874 (0.80%)
Femoral neck fracture	1/867 (0.12%)	0/874 (0.00%)
Femur fracture	5/867 (0.58%)	3/874 (0.34%)
Fibula fracture	1/867 (0.12%)	1/874 (0.11%)
Forearm fracture	1/867 (0.12%)	0/874 (0.00%)
Foreign body	1/867 (0.12%)	0/874 (0.00%)
Fracture	1/867 (0.12%)	1/874 (0.11%)
Hand fracture	0/867 (0.00%)	1/874 (0.11%)
Heat exhaustion	0/867 (0.00%)	1/874 (0.11%)
Hip fracture	12/867 (1.38%)	10/874 (1.14%)
Humerus fracture	2/867 (0.23%)	0/874 (0.00%)
Injury	1/867 (0.12%)	0/874 (0.00%)
Joint sprain	0/867 (0.00%)	1/874 (0.11%)
Laceration	4/867 (0.46%)	1/874 (0.11%)
Ligament rupture	0/867 (0.00%)	1/874 (0.11%)
Limb crushing injury	1/867 (0.12%)	0/874 (0.00%)
Limb injury	1/867 (0.12%)	0/874 (0.00%)
Lower limb fracture	1/867 (0.12%)	0/874 (0.00%)
Lumbar vertebral fracture	0/867 (0.00%)	1/874 (0.11%)
Meniscus lesion	0/867 (0.00%)	1/874 (0.11%)
Overdose	0/867 (0.00%)	1/874 (0.11%)
Pelvic fracture	2/867 (0.23%)	1/874 (0.11%)
Periorbital haematoma	1/867 (0.12%)	0/874 (0.00%)
Rib fracture	4/867 (0.46%)	2/874 (0.23%)
Road traffic accident	1/867 (0.12%)	1/874 (0.11%)
Spinal compression fracture	1/867 (0.12%)	0/874 (0.00%)
Sternal fracture	0/867 (0.00%)	1/874 (0.11%)
Stress fracture	0/867 (0.00%)	1/874 (0.11%)
Subdural haematoma	3/867 (0.35%)	2/874 (0.23%)
Subdural haemorrhage	1/867 (0.12%)	0/874 (0.00%)
Tendon injury	2/867 (0.23%)	0/874 (0.00%)
Tendon rupture	0/867 (0.00%)	1/874 (0.11%)
Thoracic vertebral fracture	0/867 (0.00%)	1/874 (0.11%)
Tibia fracture	1/867 (0.12%)	3/874 (0.34%)
Ulna fracture	1/867 (0.12%)	0/874 (0.00%)
Upper limb fracture	1/867 (0.12%)	0/874 (0.00%)
Investigations
Blood sodium decreased	0/867 (0.00%)	1/874 (0.11%)
Catheterisation cardiac	1/867 (0.12%)	0/874 (0.00%)
Heart rate irregular	1/867 (0.12%)	1/874 (0.11%)
Hepatic enzyme increased	1/867 (0.12%)	0/874 (0.00%)
Investigation	0/867 (0.00%)	1/874 (0.11%)
Medical observation	0/867 (0.00%)	1/874 (0.11%)
Prostatic specific antigen increased	0/867 (0.00%)	1/874 (0.11%)
Weight decreased	2/867 (0.23%)	0/874 (0.00%)
Metabolism and nutrition disorders
Dehydration	2/867 (0.23%)	2/874 (0.23%)
Diabetes mellitus	1/867 (0.12%)	0/874 (0.00%)
Failure to thrive	0/867 (0.00%)	1/874 (0.11%)
Hypercalcaemia	0/867 (0.00%)	1/874 (0.11%)
Hypokalaemia	2/867 (0.23%)	0/874 (0.00%)
Hyponatraemia	1/867 (0.12%)	1/874 (0.11%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/867 (0.81%)	3/874 (0.34%)
Arthritis	6/867 (0.69%)	13/874 (1.49%)
Back pain	1/867 (0.12%)	3/874 (0.34%)
Cervical spinal stenosis	1/867 (0.12%)	0/874 (0.00%)
Exostosis	0/867 (0.00%)	1/874 (0.11%)
Fall	1/867 (0.12%)	0/874 (0.00%)
Intervertebral disc degeneration	2/867 (0.23%)	2/874 (0.23%)
Intervertebral disc protrusion	9/867 (1.04%)	0/874 (0.00%)
Joint instability	1/867 (0.12%)	0/874 (0.00%)
Lumbar spinal stenosis	3/867 (0.35%)	11/874 (1.26%)
Muscle contracture	1/867 (0.12%)	0/874 (0.00%)
Musculoskeletal pain	1/867 (0.12%)	2/874 (0.23%)
Musculoskeletal stiffness	1/867 (0.12%)	0/874 (0.00%)
Osteoarthritis	16/867 (1.85%)	15/874 (1.72%)
Rhabdomyolysis	2/867 (0.23%)	0/874 (0.00%)
Rotator cuff syndrome	2/867 (0.23%)	1/874 (0.11%)
Scoliosis	2/867 (0.23%)	1/874 (0.11%)
Spinal column stenosis	11/867 (1.27%)	4/874 (0.46%)
Spinal disorder	1/867 (0.12%)	0/874 (0.00%)
Spinal osteoarthritis	2/867 (0.23%)	2/874 (0.23%)
Spondylolisthesis	2/867 (0.23%)	2/874 (0.23%)
Tendonitis	1/867 (0.12%)	0/874 (0.00%)
Vertebral foraminal stenosis	1/867 (0.12%)	0/874 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/867 (0.12%)	0/874 (0.00%)
Benign neoplasm	0/867 (0.00%)	1/874 (0.11%)
Bile duct cancer	0/867 (0.00%)	1/874 (0.11%)
Bladder cancer	2/867 (0.23%)	1/874 (0.11%)
Bladder cancer recurrent	1/867 (0.12%)	1/874 (0.11%)
Bladder transitional cell carcinoma	1/867 (0.12%)	0/874 (0.00%)
Brain neoplasm	0/867 (0.00%)	1/874 (0.11%)
Breast cancer	2/867 (0.23%)	1/874 (0.11%)
Breast cancer metastatic	1/867 (0.12%)	0/874 (0.00%)
Carcinoid tumour of the pancreas	0/867 (0.00%)	1/874 (0.11%)
Cervix carcinoma	1/867 (0.12%)	0/874 (0.00%)
Chordoma	1/867 (0.12%)	0/874 (0.00%)
Colon cancer	3/867 (0.35%)	1/874 (0.11%)
Colorectal cancer	0/867 (0.00%)	1/874 (0.11%)
Endometrial cancer	1/867 (0.12%)	0/874 (0.00%)
Gastrointestinal stromal tumour	1/867 (0.12%)	0/874 (0.00%)
Glioblastoma multiforme	1/867 (0.12%)	0/874 (0.00%)
Hepatic neoplasm	0/867 (0.00%)	1/874 (0.11%)
Hepatic neoplasm malignant	1/867 (0.12%)	0/874 (0.00%)
Large cell carcinoma of the respiratory tract stage unspecified	1/867 (0.12%)	0/874 (0.00%)
Leukaemia plasmacytic	1/867 (0.12%)	0/874 (0.00%)
Lung cancer metastatic	2/867 (0.23%)	0/874 (0.00%)
Lung neoplasm	1/867 (0.12%)	0/874 (0.00%)
Lung neoplasm malignant	1/867 (0.12%)	1/874 (0.11%)
Malignant melanoma	3/867 (0.35%)	0/874 (0.00%)
Mantle cell lymphoma	1/867 (0.12%)	0/874 (0.00%)
Metastases to meninges	0/867 (0.00%)	1/874 (0.11%)
Metastasis	0/867 (0.00%)	1/874 (0.11%)
Metastatic neoplasm	1/867 (0.12%)	0/874 (0.00%)
Multiple myeloma	1/867 (0.12%)	0/874 (0.00%)
Non-Hodgkin's lymphoma stage IV	1/867 (0.12%)	0/874 (0.00%)
Ovarian cancer	0/867 (0.00%)	2/874 (0.23%)
Pancreatic carcinoma	1/867 (0.12%)	1/874 (0.11%)
Prostate cancer	3/867 (0.35%)	2/874 (0.23%)
Rectal cancer	1/867 (0.12%)	0/874 (0.00%)
Rectosigmoid cancer	0/867 (0.00%)	1/874 (0.11%)
Renal cell carcinoma	3/867 (0.35%)	0/874 (0.00%)
Small cell lung cancer stage unspecified	1/867 (0.12%)	0/874 (0.00%)
Squamous cell carcinoma	2/867 (0.23%)	0/874 (0.00%)
T-cell lymphoma	1/867 (0.12%)	0/874 (0.00%)
Thyroid cancer	0/867 (0.00%)	1/874 (0.11%)
Nervous system disorders
Amyotrophic lateral sclerosis	0/867 (0.00%)	1/874 (0.11%)
Carotid artery occlusion	0/867 (0.00%)	2/874 (0.23%)
Carotid artery stenosis	0/867 (0.00%)	1/874 (0.11%)
Cerebellar haemorrhage	0/867 (0.00%)	1/874 (0.11%)
Cerebral haemorrhage	1/867 (0.12%)	0/874 (0.00%)
Cerebral infarction	3/867 (0.35%)	0/874 (0.00%)
Cerebrovascular accident	6/867 (0.69%)	6/874 (0.69%)
Cognitive disorder	1/867 (0.12%)	0/874 (0.00%)
Convulsion	0/867 (0.00%)	1/874 (0.11%)
Dementia	1/867 (0.12%)	0/874 (0.00%)
Dementia Alzheimer's type	1/867 (0.12%)	0/874 (0.00%)
Dizziness	5/867 (0.58%)	1/874 (0.11%)
Dysarthria	0/867 (0.00%)	1/874 (0.11%)
Encephalopathy	0/867 (0.00%)	1/874 (0.11%)
Epilepsy	1/867 (0.12%)	0/874 (0.00%)
Facial palsy	1/867 (0.12%)	1/874 (0.11%)
Grand mal convulsion	0/867 (0.00%)	1/874 (0.11%)
Guillain-Barre syndrome	0/867 (0.00%)	1/874 (0.11%)
Haemorrhagic stroke	2/867 (0.23%)	0/874 (0.00%)
Headache	1/867 (0.12%)	0/874 (0.00%)
Hypoaesthesia	1/867 (0.12%)	0/874 (0.00%)
Intracranial hypotension	1/867 (0.12%)	0/874 (0.00%)
Ischaemic stroke	2/867 (0.23%)	0/874 (0.00%)
Lethargy	0/867 (0.00%)	1/874 (0.11%)
Loss of consciousness	2/867 (0.23%)	3/874 (0.34%)
Migraine	1/867 (0.12%)	1/874 (0.11%)
Migraine with aura	0/867 (0.00%)	1/874 (0.11%)
Motor dysfunction	0/867 (0.00%)	1/874 (0.11%)
Multiple sclerosis relapse	1/867 (0.12%)	0/874 (0.00%)
Nerve compression	1/867 (0.12%)	1/874 (0.11%)
Neuropathy peripheral	1/867 (0.12%)	0/874 (0.00%)
Parkinson's disease	4/867 (0.46%)	4/874 (0.46%)
Presyncope	3/867 (0.35%)	2/874 (0.23%)
Sciatica	1/867 (0.12%)	0/874 (0.00%)
Spinal cord compression	1/867 (0.12%)	0/874 (0.00%)
Spinal cord disorder	1/867 (0.12%)	0/874 (0.00%)
Subarachnoid haemorrhage	2/867 (0.23%)	0/874 (0.00%)
Syncope	15/867 (1.73%)	12/874 (1.37%)
Transient ischaemic attack	6/867 (0.69%)	4/874 (0.46%)
Tremor	2/867 (0.23%)	0/874 (0.00%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/867 (0.12%)	0/874 (0.00%)
Psychiatric disorders
Aggression	1/867 (0.12%)	0/874 (0.00%)
Anxiety	3/867 (0.35%)	1/874 (0.11%)
Confusional state	3/867 (0.35%)	2/874 (0.23%)
Delusion	1/867 (0.12%)	1/874 (0.11%)
Depression	2/867 (0.23%)	1/874 (0.11%)
Disorientation	0/867 (0.00%)	1/874 (0.11%)
Food aversion	1/867 (0.12%)	0/874 (0.00%)
Hallucination	3/867 (0.35%)	3/874 (0.34%)
Hallucination, visual	1/867 (0.12%)	0/874 (0.00%)
Intentional self-injury	1/867 (0.12%)	0/874 (0.00%)
Major depression	0/867 (0.00%)	1/874 (0.11%)
Mania	1/867 (0.12%)	0/874 (0.00%)
Mental disorder	2/867 (0.23%)	1/874 (0.11%)
Mental status changes	1/867 (0.12%)	0/874 (0.00%)
Panic attack	0/867 (0.00%)	1/874 (0.11%)
Paranoia	1/867 (0.12%)	0/874 (0.00%)
Psychotic disorder	1/867 (0.12%)	1/874 (0.11%)
Suicidal ideation	0/867 (0.00%)	2/874 (0.23%)
Renal and urinary disorders
Bladder disorder	0/867 (0.00%)	1/874 (0.11%)
Bladder prolapse	2/867 (0.23%)	3/874 (0.34%)
Contracted bladder	0/867 (0.00%)	1/874 (0.11%)
Nephrolithiasis	6/867 (0.69%)	2/874 (0.23%)
Renal colic	2/867 (0.23%)	0/874 (0.00%)
Renal failure	1/867 (0.12%)	0/874 (0.00%)
Renal failure acute	1/867 (0.12%)	0/874 (0.00%)
Ureteric stenosis	0/867 (0.00%)	1/874 (0.11%)
Urinary incontinence	0/867 (0.00%)	1/874 (0.11%)
Urinary retention	4/867 (0.46%)	1/874 (0.11%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/867 (0.23%)	3/874 (0.34%)
Cystocele	2/867 (0.23%)	2/874 (0.23%)
Epididymitis	0/867 (0.00%)	1/874 (0.11%)
Joint dislocation	0/867 (0.00%)	1/874 (0.11%)
Ovarian cyst	1/867 (0.12%)	0/874 (0.00%)
Prostatitis	1/867 (0.12%)	1/874 (0.11%)
Prostatomegaly	4/867 (0.46%)	0/874 (0.00%)
Rectocele	1/867 (0.12%)	0/874 (0.00%)
Uterine polyp	0/867 (0.00%)	1/874 (0.11%)
Uterine prolapse	1/867 (0.12%)	0/874 (0.00%)
Vaginal prolapse	1/867 (0.12%)	1/874 (0.11%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/867 (0.00%)	1/874 (0.11%)
Atelectasis	1/867 (0.12%)	0/874 (0.00%)
Chest Pain	0/867 (0.00%)	1/874 (0.11%)
Chronic obstructive pulmonary disease	1/867 (0.12%)	0/874 (0.00%)
Cough	1/867 (0.12%)	0/874 (0.00%)
Dyspnoea	6/867 (0.69%)	2/874 (0.23%)
Laryngospasm	1/867 (0.12%)	0/874 (0.00%)
Pleural effusion	0/867 (0.00%)	2/874 (0.23%)
Pneumonia aspiration	4/867 (0.46%)	2/874 (0.23%)
Pneumothorax	2/867 (0.23%)	0/874 (0.00%)
Pulmonary embolism	11/867 (1.27%)	7/874 (0.80%)
Pulmonary interstitial emphysema syndrome	0/867 (0.00%)	1/874 (0.11%)
Respiratory arrest	1/867 (0.12%)	0/874 (0.00%)
Skin and subcutaneous tissue disorders
Angioedema	1/867 (0.12%)	1/874 (0.11%)
Surgical and medical procedures
Angioplasty	1/867 (0.12%)	0/874 (0.00%)
Aortic valve replacement	3/867 (0.35%)	0/874 (0.00%)
Appendicectomy	0/867 (0.00%)	1/874 (0.11%)
Benign tumour excision	1/867 (0.12%)	0/874 (0.00%)
Cardiac pacemaker insertion	0/867 (0.00%)	2/874 (0.23%)
Cholecystectomy	0/867 (0.00%)	3/874 (0.34%)
Colporrhaphy	0/867 (0.00%)	1/874 (0.11%)
Deep brain stimulation	27/867 (3.11%)	24/874 (2.75%)
Heart valve replacement	1/867 (0.12%)	0/874 (0.00%)
Hernia hiatus repair	0/867 (0.00%)	1/874 (0.11%)
Hernia repair	1/867 (0.12%)	1/874 (0.11%)
Hip arthroplasty	5/867 (0.58%)	2/874 (0.23%)
Hysterectomy	2/867 (0.23%)	3/874 (0.34%)
Joint arthroplasty	1/867 (0.12%)	5/874 (0.57%)
Knee arthroplasty	5/867 (0.58%)	3/874 (0.34%)
Large intestine anastomosis	0/867 (0.00%)	1/874 (0.11%)
Meniscus operation	0/867 (0.00%)	1/874 (0.11%)
Mitral valve replacement	1/867 (0.12%)	0/874 (0.00%)
Nephrectomy	1/867 (0.12%)	1/874 (0.11%)
Prophylaxis of nausea and vomiting	0/867 (0.00%)	1/874 (0.11%)
Prostatectomy	0/867 (0.00%)	1/874 (0.11%)
Shoulder arthroplasty	0/867 (0.00%)	1/874 (0.11%)
Spinal decompression	1/867 (0.12%)	0/874 (0.00%)
Spinal fusion surgery	2/867 (0.23%)	3/874 (0.34%)
Spinal laminectomy	1/867 (0.12%)	3/874 (0.34%)
Stent placement	2/867 (0.23%)	2/874 (0.23%)
Surgery	1/867 (0.12%)	2/874 (0.23%)
Thalamotomy	1/867 (0.12%)	0/874 (0.00%)
Thyroidectomy	1/867 (0.12%)	0/874 (0.00%)
Tracheostomy	1/867 (0.12%)	0/874 (0.00%)
Transurethral prostatectomy	1/867 (0.12%)	2/874 (0.23%)
Vascular disorders
Aneurysm	1/867 (0.12%)	0/874 (0.00%)
Aortic aneurysm	3/867 (0.35%)	1/874 (0.11%)
Aortic dissection	1/867 (0.12%)	0/874 (0.00%)
Aortic occlusion	0/867 (0.00%)	1/874 (0.11%)
Aortic stenosis	1/867 (0.12%)	0/874 (0.00%)
Arterial stenosis	1/867 (0.12%)	0/874 (0.00%)
Deep vein thrombosis	0/867 (0.00%)	6/874 (0.69%)
Embolism	0/867 (0.00%)	1/874 (0.11%)
Fibromuscular dysplasia	0/867 (0.00%)	1/874 (0.11%)
Hypertension	4/867 (0.46%)	0/874 (0.00%)
Hypertensive crisis	1/867 (0.12%)	0/874 (0.00%)
Hypotension	3/867 (0.35%)	2/874 (0.23%)
Orthostatic hypotension	2/867 (0.23%)	3/874 (0.34%)
Thrombosis	1/867 (0.12%)	1/874 (0.11%)
Venous thrombosis	0/867 (0.00%)	1/874 (0.11%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Creatine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	687/867 (79.24%)	698/874 (79.86%)
Eye disorders
Cataract	51/867 (5.88%)	44/874 (5.03%)
Gastrointestinal disorders
Constipation	107/867 (12.34%)	121/874 (13.84%)
Diarrhoea	50/867 (5.77%)	65/874 (7.44%)
Gastrooesophageal reflux disease	53/867 (6.11%)	39/874 (4.46%)
Nausea	101/867 (11.65%)	99/874 (11.33%)
Pain	122/867 (14.07%)	121/874 (13.84%)
General disorders
Fatigue	47/867 (5.42%)	48/874 (5.49%)
Oedema	139/867 (16.03%)	154/874 (17.62%)
Infections and infestations
Sinusitis	46/867 (5.31%)	55/874 (6.29%)
Upper respiratory tract infection	63/867 (7.27%)	66/874 (7.55%)
Urinary tract infection	109/867 (12.57%)	85/874 (9.73%)
Injury, poisoning and procedural complications
Fall	97/867 (11.19%)	91/874 (10.41%)
Investigations
Weight decreased	50/867 (5.77%)	35/874 (4.00%)
Weight increased	101/867 (11.65%)	137/874 (15.68%)
Musculoskeletal and connective tissue disorders
Arthralgia	64/867 (7.38%)	81/874 (9.27%)
Back pain	106/867 (12.23%)	105/874 (12.01%)
Muscle spasms	53/867 (6.11%)	101/874 (11.56%)
Musculoskeletal pain	45/867 (5.19%)	43/874 (4.92%)
Pain in extremity	31/867 (3.58%)	47/874 (5.38%)
Nervous system disorders
Dizziness	81/867 (9.34%)	62/874 (7.09%)
Somnolence	67/867 (7.73%)	61/874 (6.98%)
Psychiatric disorders
Anxiety	77/867 (8.88%)	65/874 (7.44%)
Depression	106/867 (12.23%)	100/874 (11.44%)
Hallucination	39/867 (4.50%)	45/874 (5.15%)
Insomnia	101/867 (11.65%)	96/874 (10.98%)
Renal and urinary disorders
Pollakiuria	50/867 (5.77%)	34/874 (3.89%)
Proteinuria	49/867 (5.65%)	47/874 (5.38%)
Vascular disorders
Hypertension	46/867 (5.31%)	46/874 (5.26%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Karl Kieburtz, Director of CTSI
Organization:	University of Rochester
Phone:	585-275-0553
EMail:	Karl.kieburtz@chet.rochester.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Leehey M, Luo S, Sharma S, Wills AA, Bainbridge JL, Wong PS, Simon DK, Schneider J, Zhang Y, Pérez A, Dhall R, Christine CW, Singer C, Cambi F, Boyd JT. Association of metabolic syndrome and change in Unified Parkinson's Disease Rating Scale scores. Neurology. 2017 Oct 24;89(17):1789-1794. doi: 10.1212/WNL.0000000000004572. Epub 2017 Sep 29.

Wills AM, Li R, Pérez A, Ren X, Boyd J; NINDS NET-PD Investigators. Predictors of weight loss in early treated Parkinson's disease from the NET-PD LS-1 cohort. J Neurol. 2017 Aug;264(8):1746-1753. doi: 10.1007/s00415-017-8562-4. Epub 2017 Jul 15.

Augustine EF, Dorsey ER, Hauser RA, Elm JJ, Tilley BC, Kieburtz KK. Communicating with participants during the conduct of multi-center clinical trials. Clin Trials. 2016 Dec;13(6):592-596. Epub 2016 Aug 29.

Wills AM, Pérez A, Wang J, Su X, Morgan J, Rajan SS, Leehey MA, Pontone GM, Chou KL, Umeh C, Mari Z, Boyd J; NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators. Association Between Change in Body Mass Index, Unified Parkinson's Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease: Secondary Analysis of Longitudinal Data From NINDS Exploratory Trials in Parkinson Disease Long-term Study 1. JAMA Neurol. 2016 Mar;73(3):321-8. doi: 10.1001/jamaneurol.2015.4265.

Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators, Kieburtz K, Tilley BC, Elm JJ, Babcock D, Hauser R, Ross GW, Augustine AH, Augustine EU, Aminoff MJ, Bodis-Wollner IG, Boyd J, Cambi F, Chou K, Christine CW, Cines M, Dahodwala N, Derwent L, Dewey RB Jr, Hawthorne K, Houghton DJ, Kamp C, Leehey M, Lew MF, Liang GS, Luo ST, Mari Z, Morgan JC, Parashos S, Pérez A, Petrovitch H, Rajan S, Reichwein S, Roth JT, Schneider JS, Shannon KM, Simon DK, Simuni T, Singer C, Sudarsky L, Tanner CM, Umeh CC, Williams K, Wills AM. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. JAMA. 2015 Feb 10;313(6):584-93. doi: 10.1001/jama.2015.120.

Layout table for additonal information

Responsible Party:	Karl Kieburtz, University of Rochester
ClinicalTrials.gov Identifier:	NCT00449865
Other Study ID Numbers:	U01NS43128 NET-PD CRC
First Submitted:	March 20, 2007
First Posted:	March 21, 2007
Results First Submitted:	February 19, 2015
Results First Posted:	April 2, 2015
Last Update Posted:	April 2, 2015

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