Ignite Creation Date:
2024-05-05 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00140166
Status:
COMPLETED
Last Update Posted:
2009-11-25
First Post:
2005-08-31
Brief Title:
Treatment of Acute Schizophrenia With Vitamin Therapy
Sponsor:
Beersheva Mental Health Center
Organization:
Beersheva Mental Health Center
Study Overview
Official Title:
The Treatment of Acute Schizophrenia With High Dose Niacinmide Plus Ascorbate Plus Pyridoxine Plus Centrum Forte vs Centrum Forte Only as an Add-On to Risperidone and Dietary Counseling
Status:
COMPLETED
Status Verified Date:
2009-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Controlled studies using the orthomolecular approach have been few Deutsch Ananth Ban 1977 Those that were done were performed in chronic schizophrenia or in populations that included bipolar and schizoaffective patients Both of these diagnostic groups are not today considered to benefit from the orthomolecular approach Moreover some negative studies of high-dose niacin were done in patients who were not otherwise given general counseling for good diet as described above Therefore this proposal is to study in a controlled manner carefully defined first onset schizophrenic patients using the protocol advocated by Osmond and Hoffer 1962 Patients can enter the study if they have been ill less than 1 year and are in their first hospitalization
Detailed Description:
Controlled studies using the orthomolecular approach have been few Deutsch Ananth Ban 1977 Those that were done were performed in chronic schizophrenia or in populations that included bipolar and schizoaffective patients Both of these diagnostic groups are not today considered to benefit from the orthomolecular approach Moreover some negative studies of high-dose niacin were done in patients who were not otherwise given general counseling for good diet as described above Therefore this proposal is to study in a controlled manner carefully defined first onset schizophrenic patients using the protocol advocated by Osmond and Hoffer 1962 Patients can enter the study if they have been ill less than 1 year and are in their first hospitalization Our Beersheba Mental Health Center is the only hospitalization facility for Southern Israel population of half a million There about 2 thousand admissions to our hospital yearly and of those there are over 100 admissions with a diagnosis of schizophrenia or schizophreniform disorder for whom this is the first lifetime admission to hospital and their first episode of psychosis
Methods Study I - Open Pilot The pilot study will be carried out exactly as below except without a control group Results from the pilot will be evaluated before continuing to the controlled study and protocol modifications presented to the Helsinki Committee if necessary Ten patients will be studied in this open pilot study
Study II - Controlled Study Not Blind Inclusion and exclusion criteria Patients can be accepted to the study age 18-30 if admitting diagnosis after review by the study coordinator is schizophrenia or schizophreniform disorder by DSM-IV Since the diagnosis of schizophrenia may be difficult in the early stages of acute psychotic disease cases in which the clinical diagnosis is consistent with and suspicious of schizophrenia and inconsistent with bipolar disorder even if they do not fulfill all the diagnostic criteria in DSM-IV will be accepted Patients with alcohol or drug abuse in the last 6 months will be excluded Patients with significant physical illness including peptic ulcer or a history of hepatitis or baseline abnormal liver function tests will be excluded Patients with mental retardation will be excluded Baseline screening will be done for liver function including AST bilirubin alkaline phosphatase and LDH and blood glucose and then repeated after 6 weeks Elevations of AST over three fold will lead to dropping patient from study Patients who are unlikely to be able to continue in the study as outpatients will be excluded Patients will be admitted to study only if this is their first lifetime psychiatric admission and their first episode of psychosis and only if history supports that they have been mentally ill for less than one year
Procedure Patients who enter the program will be treated with risperidone 2-8mg daily at physicians discretion They will be randomized according to a predetermined random order to vitamin regime or Centrum forte Doses of risperidone will be lowered as clinically possible Risperidone dose will be recorded weekly and will serve as a secondary outcome measure A registered dietician will meet with each patient weekly and discourage refined sugar or excess fat and encourage regular fruit and vegetable consumption High protein breakfast will be emphasized Fifteen patients will be started yearly for three years
The vitamin regimen will be as follows twice daily with food
1 Ascorbic acid 15 g twice daily
2 150 mg vitamin B6 twice daily
3 Niacinamide 500 mg tablets 3 tablets 15g twice daily with food
4 Centrum Forte one tablet each morning with food
The comparison group will receive Centrum Forte once per day
Outcome measures
Patients will be rated with the Brief Psychiatric Rating Scale BPRS at baseline and weekly for 6 months All patients will receive supportive psychotherapy both during the hospitalization and in clinic follow-up Discharged patients will be followed in the outpatient clinic of the Beersheba Mental Health Center by a physician plus dietician team dedicated to this study Each patient will be followed for six months Outcome measures will be BPRS ratings over the course of the half year readmissions Global Clinical Assessment of function at the end of the half year and risperidone dose
Skin test A blunted response of dermal erythema to niacin has been widely reported in schizophrenia and it is possible that this response might predict clinical response to niacin treatment All patients will have the Horrobin niacin patch test Smesny et al 2003 on admission to the study and it will be repeated after 6 months of continuous therapy Niacin is applied simultaneously in four dilutions 01 001 0001 00001M of 50microl each approximately one drop of a standard eye-dropper to the skin at the inner side of the forearm using chambered plaster for epicutaneous testing After 90 seconds the plaster is removed Skin reaction is quantitated at 3 minute intervals up to 21 minutes starting 90 seconds after removal of the plaster
Risks The risks of high dose ascorbic acid have been reviewed extensively but these refer to doses such as 10g daily and the present dose of 3g daily is associated with minimal risk eg diarrhea Doses greater than 3gm daily can cause increases in ALT and uric acid but risk of kidney stones has not been substantiated Russel 2005 Niacin at 3g daily is now widely used as a cholesterol lowering agent Alpers Stenson Bier 2002 and is associated with minimal side effects or dangers eg up to 5 increased glucose elevations of liver enzymes and exacerbation in peptic ulcer but these effects are rarely if ever seen with the derivative nicotinamide Guyton 2005 The other B-vitamins in the doses given would not be associated with any side effects
Alpers D H Stenson W F Bier D M 2002 Manual of Nutritional Therapeutics Philadelphia Lippincott Williams Wilkins
Beauclair L Vinogradov S Riney S J Csernansky J G Hollister L E 1987 An adjunctive role for ascorbic acid in the treatment of schizophrenia J Clin Psychopharmacol 74 282-283
Deutsch M Ananth J V Ban T A 1977 Nicotinic acid in the treatment of chronic hospitalized schizophrenic patients a placebo-controlled clinical study Psychopharmacol Bull 133 21-23
Guyton J R 2005 Hyperlimpprotenemias In R E Rakel E T Bope Eds Conns Current Therapy 2005 pp 688-694 Pennsylvania ElsevierSaunders
Kanofsky J D Sandyk R 1992 Antioxidants in the treatment of schizophrenia Int J Neurosci 621-2 97-100
Kleijnen J Knipschild P 1991 Niacin and vitamin B6 in mental functioning a review of controlled trials in humans Biol Psychiatry 299 931-941
Lerner V Miodownik C Kaptsan A Cohen H Loewenthal U Kotler M 2002 Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients a double-blind placebo-controlled study J Clin Psychiatry 631 54-58
Levine J Stahl Z Sela B A Ruderman V Shumaico O Babushkin I et al under revision Homocysteine reducing strategies improve symptoms in chronic schizophrenia patients with hyperhomocysteinemia
Osmond H Hoffer A 1962 Massive niacin treatment in schizophrenia Review of a nine-year study Lancet 1 316-319
Russel R M 2005 Vitamine and trace mineral deficiency and excess In D L Kasper A S Favci D L Lango E Braunwald S L Hauser J L Jameson Eds Harrisons Principles of Internal Medicine 16th ed pp 403-407 McGraw Hill
Sandyk R Kanofsky J D 1993 Vitamin C in the treatment of schizophrenia Int J Neurosci 681-2 67-71
Smesny S Berger G Rosburg T Riemann S Riehemann S McGorry P et al 2003 Potential use of the topical niacin skin test in early psychosis -- a combined approach using optical reflection spectroscopy and a descriptive rating scale J Psychiatr Res 373 237-247
Smythies J R 1996 The role of ascorbate in brain therapeutic implications J R Soc Med 895 241
Straw G M Bigelow L B Kirch D G 1989 Haloperidol and reduced haloperidol concentrations and psychiatric ratings in schizophrenic patients treated with ascorbic acid J Clin Psychopharmacol 92 130-132
Suboticanec K Folnegovic-Smalc V Korbar M Mestrovic B Buzina R 1990 Vitamin C status in chronic schizophrenia Biol Psychiatry 2811 959-966
Suboticanec K Folnegovic-Smalc V Turcin R Mestrovic B Buzina R 1986 Plasma levels and urinary vitamin C excretion in schizophrenic patients Hum Nutr Clin Nutr 406 421-428
Vaughan K McConaghy N 1999 Megavitamin and dietary treatment in schizophrenia a randomised controlled trial Aust N Z J Psychiatry 331 84-88
Methods Study I - Open Pilot The pilot study will be carried out exactly as below except without a control group Results from the pilot will be evaluated before continuing to the controlled study and protocol modifications presented to the Helsinki Committee if necessary Ten patients will be studied in this open pilot study
Study II - Controlled Study Not Blind Inclusion and exclusion criteria Patients can be accepted to the study age 18-30 if admitting diagnosis after review by the study coordinator is schizophrenia or schizophreniform disorder by DSM-IV Since the diagnosis of schizophrenia may be difficult in the early stages of acute psychotic disease cases in which the clinical diagnosis is consistent with and suspicious of schizophrenia and inconsistent with bipolar disorder even if they do not fulfill all the diagnostic criteria in DSM-IV will be accepted Patients with alcohol or drug abuse in the last 6 months will be excluded Patients with significant physical illness including peptic ulcer or a history of hepatitis or baseline abnormal liver function tests will be excluded Patients with mental retardation will be excluded Baseline screening will be done for liver function including AST bilirubin alkaline phosphatase and LDH and blood glucose and then repeated after 6 weeks Elevations of AST over three fold will lead to dropping patient from study Patients who are unlikely to be able to continue in the study as outpatients will be excluded Patients will be admitted to study only if this is their first lifetime psychiatric admission and their first episode of psychosis and only if history supports that they have been mentally ill for less than one year
Procedure Patients who enter the program will be treated with risperidone 2-8mg daily at physicians discretion They will be randomized according to a predetermined random order to vitamin regime or Centrum forte Doses of risperidone will be lowered as clinically possible Risperidone dose will be recorded weekly and will serve as a secondary outcome measure A registered dietician will meet with each patient weekly and discourage refined sugar or excess fat and encourage regular fruit and vegetable consumption High protein breakfast will be emphasized Fifteen patients will be started yearly for three years
The vitamin regimen will be as follows twice daily with food
1 Ascorbic acid 15 g twice daily
2 150 mg vitamin B6 twice daily
3 Niacinamide 500 mg tablets 3 tablets 15g twice daily with food
4 Centrum Forte one tablet each morning with food
The comparison group will receive Centrum Forte once per day
Outcome measures
Patients will be rated with the Brief Psychiatric Rating Scale BPRS at baseline and weekly for 6 months All patients will receive supportive psychotherapy both during the hospitalization and in clinic follow-up Discharged patients will be followed in the outpatient clinic of the Beersheba Mental Health Center by a physician plus dietician team dedicated to this study Each patient will be followed for six months Outcome measures will be BPRS ratings over the course of the half year readmissions Global Clinical Assessment of function at the end of the half year and risperidone dose
Skin test A blunted response of dermal erythema to niacin has been widely reported in schizophrenia and it is possible that this response might predict clinical response to niacin treatment All patients will have the Horrobin niacin patch test Smesny et al 2003 on admission to the study and it will be repeated after 6 months of continuous therapy Niacin is applied simultaneously in four dilutions 01 001 0001 00001M of 50microl each approximately one drop of a standard eye-dropper to the skin at the inner side of the forearm using chambered plaster for epicutaneous testing After 90 seconds the plaster is removed Skin reaction is quantitated at 3 minute intervals up to 21 minutes starting 90 seconds after removal of the plaster
Risks The risks of high dose ascorbic acid have been reviewed extensively but these refer to doses such as 10g daily and the present dose of 3g daily is associated with minimal risk eg diarrhea Doses greater than 3gm daily can cause increases in ALT and uric acid but risk of kidney stones has not been substantiated Russel 2005 Niacin at 3g daily is now widely used as a cholesterol lowering agent Alpers Stenson Bier 2002 and is associated with minimal side effects or dangers eg up to 5 increased glucose elevations of liver enzymes and exacerbation in peptic ulcer but these effects are rarely if ever seen with the derivative nicotinamide Guyton 2005 The other B-vitamins in the doses given would not be associated with any side effects
Alpers D H Stenson W F Bier D M 2002 Manual of Nutritional Therapeutics Philadelphia Lippincott Williams Wilkins
Beauclair L Vinogradov S Riney S J Csernansky J G Hollister L E 1987 An adjunctive role for ascorbic acid in the treatment of schizophrenia J Clin Psychopharmacol 74 282-283
Deutsch M Ananth J V Ban T A 1977 Nicotinic acid in the treatment of chronic hospitalized schizophrenic patients a placebo-controlled clinical study Psychopharmacol Bull 133 21-23
Guyton J R 2005 Hyperlimpprotenemias In R E Rakel E T Bope Eds Conns Current Therapy 2005 pp 688-694 Pennsylvania ElsevierSaunders
Kanofsky J D Sandyk R 1992 Antioxidants in the treatment of schizophrenia Int J Neurosci 621-2 97-100
Kleijnen J Knipschild P 1991 Niacin and vitamin B6 in mental functioning a review of controlled trials in humans Biol Psychiatry 299 931-941
Lerner V Miodownik C Kaptsan A Cohen H Loewenthal U Kotler M 2002 Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients a double-blind placebo-controlled study J Clin Psychiatry 631 54-58
Levine J Stahl Z Sela B A Ruderman V Shumaico O Babushkin I et al under revision Homocysteine reducing strategies improve symptoms in chronic schizophrenia patients with hyperhomocysteinemia
Osmond H Hoffer A 1962 Massive niacin treatment in schizophrenia Review of a nine-year study Lancet 1 316-319
Russel R M 2005 Vitamine and trace mineral deficiency and excess In D L Kasper A S Favci D L Lango E Braunwald S L Hauser J L Jameson Eds Harrisons Principles of Internal Medicine 16th ed pp 403-407 McGraw Hill
Sandyk R Kanofsky J D 1993 Vitamin C in the treatment of schizophrenia Int J Neurosci 681-2 67-71
Smesny S Berger G Rosburg T Riemann S Riehemann S McGorry P et al 2003 Potential use of the topical niacin skin test in early psychosis -- a combined approach using optical reflection spectroscopy and a descriptive rating scale J Psychiatr Res 373 237-247
Smythies J R 1996 The role of ascorbate in brain therapeutic implications J R Soc Med 895 241
Straw G M Bigelow L B Kirch D G 1989 Haloperidol and reduced haloperidol concentrations and psychiatric ratings in schizophrenic patients treated with ascorbic acid J Clin Psychopharmacol 92 130-132
Suboticanec K Folnegovic-Smalc V Korbar M Mestrovic B Buzina R 1990 Vitamin C status in chronic schizophrenia Biol Psychiatry 2811 959-966
Suboticanec K Folnegovic-Smalc V Turcin R Mestrovic B Buzina R 1986 Plasma levels and urinary vitamin C excretion in schizophrenic patients Hum Nutr Clin Nutr 406 421-428
Vaughan K McConaghy N 1999 Megavitamin and dietary treatment in schizophrenia a randomised controlled trial Aust N Z J Psychiatry 331 84-88
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None