Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00140166 |
| Other study ID # |
BMHC-3996 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
August 31, 2005 |
| Last updated |
November 23, 2009 |
| Start date |
July 2005 |
| Est. completion date |
May 2008 |
Study information
| Verified date |
November 2009 |
| Source |
Beersheva Mental Health Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Israel: Israeli Health Ministry Pharmaceutical Administration |
| Study type |
Interventional
|
Clinical Trial 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.
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
physician's 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 1.5 g twice daily.
2. 150 mg vitamin B6 twice daily
3. Niacinamide 500 mg tablets, 3 tablets (1.5g) 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 (0.1, 0.01, 0.001, 0.0001M) 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.
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