Re: LDN Trial Proposal

[Guest guest]

would very much like a copy thank you Calvin .e mail addrest vcbowser

@turboisp.com

mboylebradley wrote:

>Hi All .. To , Lorna, Terry, Aidan, , Grace, ..

>first my address book was infected with a virus so I have lost your

>email and cannot forward the trial proposal as I had planned.

> .. Coirle has a copy so I think Galway is covered.

>I sent it to the Irish Government today .. Minister for Finance,

>Minister for Health and the Taoiseach.

>To anybody who thinks they could use a copy of the proposal for an

>interested party .. email me and I will forward it to you. It is a 12

>month trial proposal for 300 patients .. 2/3's on LDN and 1/3 on

>placebo .. costing a mere 900,000 Euro apparently. There may be

>issues there but it doesn't matter at this point .. it is Dr Bihari's

>ballpark figure.

>I think it would be great if someone from every country here took a

>copy and fired it off to their Government or any institution capable

>of helping. Dr Bihari is willing to travel to Ireland and conduct the

>trial .. all he asks for is literally flight and accomodation .. I am

>pretty sure he would extend that offer to any other country willing

>to seriously bite.

>All the Best

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[Guest guest]

I would like to see a copy of the trial protocol.

Should this be published in the net so everyone can see it?

redtruck99@...

[Guest guest]

Here is a copy of the proposal ..I am having trouble keeping up with

the requests today so everyone might as well look .. the fonts etc

won't appear here but the text is what I sent to the Irish

Government. To those that I sent a copy make sure it is the same as

this as I fear I may have sent an old version to some of you .. sorry.

The proposal is simple and to the point .. if they are interested

they will bite as it has all the detail required .. but will they

believe it is the question. Pressure is probably needed at this point.

All the Best

Multiple Sclerosis Letter of Inquiry Submission

Contact Information

Organization Name:

The Foundation of Immunological Research

Organization Address:

29 West 15th Street

New York

New York, 10011

USA

Organization Tax Status:

501©(3) public charity

Primary Contact Prefix:

Dr Bernard Bihari, MD

Title of Primary Contact:

Medical Director

Primary Contact Phone:

001 212 9294196

Primary Contact E-mail:

mboylebradley@...

Primary Contact Fax:

001 212 2299371

Narrative

Naltrexone at doses of 1.75mg to 4.5mg has been shown to stabilize

the CD4 absolute count and the CD4 percentage in people with

HIV/AIDS. It has also been shown to provide protection from HIV

disease, protection as reflected in the incidence of opportunistic

infections and HIV related deaths.. In the wake of these results Dr

Bihari discovered serendipitously that low does naltrexone (LDN)

because of it's ability to increase production of endorphins during

the night, when it is taken at bedtime (9PM to 2AM) to be useful in

the treatment of a wide range of autoimmune diseases. These diseases

apparently respond because of the role low serum endorphins and

intracellular endorphins play in their etiology, with return of

normal endorphin levels having a beneficial effect.

The autoimmune disease in which LDN is used most at present is

Multiple Sclerosis (MS). Dr Bihari currently has 384 patients with MS

in his medical care in a private practice setting in New York City.

These patients have been on LDN for an average of 2.5 years with a

range of 1 week to 19 years. The overall results of treatment with

this drug have been excellent. Only 3 of the 384 patients have shown

any attacks. To be more specific, one of these three, who started LDN

18 years ago, at the age of 22 in 1988, had one attack after 5 years

on the drug, 30 days after stopping it. The patient resumed LDN when

the attack appeared and has had none in the 13 years since. The

second of the three, a 41 year old woman had an episode of optic

neuritis which cleared in 4 weeks, after 18 months on LDN. The last

of the three was a patient who experienced an episode of numbness in

the left leg after 8 months on LDN, not previously present, which

cleared after 3 weeks. The other 381 patients with MS have had no

sign of disease activity since starting LDN.

Approximately 25% of the patients starting on 4.5mg LDN have

experienced an increase in spasticity. When the dose is reduced to

3mg the increase always clears. Overall, most patients with

significant spasticity , especially in the legs experience an overall

reduction in spasticity once the proper dose is achieved. The fatigue

associated with MS is generally reduced, sometimes substantially

after a few days on LDN. Rarely other MS symptoms are reduced while

on LDN, such as bladder spasticity and urinary incontinence and there

is an occasional patient who shows cognitive improvement if cognitive

impairment was present before treatment began.

About 20% of these patients were on avonex, beta-seron, copaxone,

novantrone or methotrexate before beginning LDN. Although no

recommendation is made about whether or not to continue these drugs

by Dr Bihari, only one has remained on copaxone with LDN for the 12

months she has been on LDN. The copaxone did not seem to interfere

with her LDN effect.

There are at present several thousand people with MS on LDN, who have

had their LDN prescribed by their physicians after reading about it

on the LDN website, www.ldninfo.org. Emails to the website as well as

emails to a number of other websites devoted to MS treatment suggests

that the response to LDN in the wider community of people with MS

approximates the clinical response in Dr Bihari's medical practice.

Background

In the light of recent evidence suggesting that the endorphinergic

system plays an important role in the homeostatic regulation of

immune function, we have developed and tested immunoenhancing

treatment using low dose naltrexone in the dosage range of 1.75 to

4.5mg. Human T-cell rosette formation is enhanced by metenkephalin

and this effect is blocked by prior or simultaneous treatment with

naltrexone, a narcotic antagonist, thus demonstrating that T-cells

have functionally important opiate receptors. Other studies have

shown that the following functions involve opiate receptors and/or

are facilitated by endorphins: lymphocyte blastogenesis, T and B cell

cooperation, lymphocyte mitogen responsiveness, in vitro antibody

response to sheep RBC'c, natural killer cell activity, expression of

cell surface markers involved in lymphocyte activation (such as

OKT10,IL2, and la receptors), monocyte chemotaxis, and macrophage

cytotoxicity. Studies indicating that virus infected lymphocytes

produce beta-endorphin, and that both Interleukin I and Interleukin

II stimulate pituitary synthesis of beta-endorphin, suggest that the

central nervous system and the immune system have complex

endorphinergic feedback loops that may be important in homeostatic

regulation of immune function.

Endorphinergic system involvement in homeostatic regulation of immune

function raises the possibility that disturbances in this system may

contribute to the pathophysiology of autoimmune diseases such as

multiple sclerosis and that endorphinergic upregulation might have an

imunoenhancing effect in its treatment.

Letter of Inquiry

Project Objective

To demonstrate LDN (low dose naltrexone) as the most effective

treatment for Multiple Sclerosis.

Project Description:

The first goal of the project is to interest a country in conducting

a full-scale, double-blind, placebo-controlled prospective study of

LDN as a treatment for MS. Then, with the successful outcome of the

clinical trial, Dr. Bihari will work to achieve these further

objectives:

1. In the country which hosted the trial, to license a capable entity—

with no licensing fee—to manufacture LDN.

2. To help ensure the general availability of LDN throughout the

world.

3. To gain scientific recognition of the efficacy of LDN for the

treatment of MS.

Trial Proposal

A 12 month placebo controlled study of LDN at 3.0mg is planned.

Recommended sample size is 300 patients, 2/3's on the drug. 1/3 on

placebo. Patients should be randomly assigned to drug or placebo. If

the trial shows efficacy the placebo patients should be offered LDN

when the trial is completed.

Patient Eligibility

Patients must be between 18 and 65 years of age with relapsing,

remitting or secondary progressive MS. Patients with primary

progressive MS may not participate.

Study Design

Patients will have initial medical and neurological history and

physical exam with review of medical records to determine if they are

eligible. All patients considered eligible should have had at least

one MRI of the brain, the spinal cord or both showing

plaques/demylenation consistent with a diagnosis of MS. On the trial

entry patients will be randomly assigned to active drug or placebo.

Patients on drug will be started at 3.0mg of LDN taken between 9PM

and 2AM. Within one week of admission to the study all patients

should receive and MRI of the brain and the spinal cord to be

repeated at the end of the study.

Study Evaluations

Patients will undergo a complete medical/neurological and physical

exam every 8 weeks for 12 months.

Monitoring Procedure

Case Report forms will be developed for entering data on admission

and on the 8 week visits. Presumably the patients will be seen on

these visits by a physician, physician's assistant or nurse

practitioner. An independent monitoring agency should collect data

from the Case Report Forms for analysis at the end of the trial.

Side Effects

Naltrexone has some mild side effects at 50mg per day. In several

thousand patients taking it at a low dose, most recently 3.0 to 4.5

mgs, no side effects or adverse reactions have been observed except

for 1-2% of patients who experience restless sleep at this dose for

brief period.

Pregnancy

No teratogenic effects have been observed with naltrexone at 50mg or

at the lower doses of 1.75 to 4.5mg. However, there is a theoretical

possibility that raising endorphins, which are always low in people

with autoimmune , might reduce birth weights of babies born to

mothers on the drug by as much as 10%. Because of this, a pregnancy

test should be done routinely in women of childbearing age applying

for admission to the study and if it is positive they should be

excluded, as should women who get pregnant during the course of the

study. This problem is probably minor and ultimately may not affect

the usefulness of the drug in pregnant women because of the

seriousness of the illness it is being used to treat. However,

pregnant women should be excluded from this trial until more

information is available about the effects of LDN on pregnancy.

Informed Consent

The investigator is responsible to ensure that each subject (or

subject's legal representative) signs an informed consent statement

prior to participation in this trial. The consent form and the whole

protocol should be reviewed and approved by an appropriate

Institutional Review Board to assure protection of patient's rights.

The signed copies of the consent forms are to be retained by the

investigator. The patients will be informed of their right to privacy

and the fact that the results will be submitted only to the study

sponsor and the appropriate department of the hospital in such a way

that the patient's identity will not be known. The Institutional

Review Board and the hospital have the right to inspect the patient's

medical record to verify the accuracy and completeness of this

trial.

Amount Requested to Complete LDN for MS Trial in Ireland

900,000 Euros

Project Duration

12 months

> I would like to see a copy of the trial protocol.

> Should this be published in the net so everyone can see it?

>

> redtruck99@y...