Heart and Blood Diseases

All Conditions

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Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Nervous System Diseases

Wounds and Injuries

Coronary Artery Disease

Myocardial Ischemia

Coronary Disease

Myocardial Infarction

Infarction

Diabetes Mellitus

Stroke

Fractures, Bone

Osteoporotic Fractures

Cerebrovascular Disorders

Brain Diseases

Central Nervous System Diseases

Vascular Diseases

Ischemia

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Heart Diseases

Micronutrients

All Drugs and Chemicals

Hematinics

Vitamins

Vitamin B 6

Pyridoxal

Pyridoxine

Folic Acid

Vitamin B Complex

Vitamin B 12

Hydroxocobalamin

Pyridoxal Phosphate

Folinic Acid

Vitamin B6

Methylcobalamin

Folate

Vitamin B9

Vitamin B12

Cobalamin

Cyanocobalamin

Participants in NORVIT and WENBIT allocated to daily oral treatment with folic acid 0.8 mg and vitamin B12 0.4 mg

Participants in NORVIT and WENBIT allocated to daily oral treatment with folic acid 0.8 mg, vitamin B12 0.4 mg and B6 40 mg.

Participants in NORVIT and WENBIT allocated to daily oral treatment with vitamin B6 40 mg.

Participants in NORVIT and WENBIT allocated to daily oral treatment with placebo

Ottar Nygård, MD, PhD

Two large homocysteine-lowering B-vitamin intervention trials have been performed in Norway during the period 1998 to 2005, NORVIT and WENBIT. The main objective in these trials was to study the clinical effects of homocysteine-lowering therapy with folic acid and vitamin B12 in patients with established coronary artery disease. Follow-up was terminated for NORVIT on Marc 31st 2004 and for WENBIT October 5th 2005, and none of the two trials proved any protective effect of the B-vitamin intervention on cardiovascular outcomes.

There is so far no data on possible long-term effects following years of such B-vitamin treatment.

Thus, the main objective of the combinded NORVIT-WENBIT study will will be to evaluate the long-term effect of the B-vitamin intervention on incident life-style diseases including cardiovascular disease, diabetes, osteoporotic fractures and cancer.

A secondary object will be the identification of risk phenotypes or genotypes, and if such risk associations are midified by the B-vitamin intervention

The "homocysteine-hypothesis" of vascular disease has attracted considerable interest, as total plasma homocysteine levels can be easily lowered by folic acid and vitamin B12, raising the prospect that cardiovascular disease could be lowered by such B-vitamin supplementation.

Two large B-vitamin intervention trials have been performed in Norway during the period 1998 to 2005, NORVIT and WENBIT, both registered at ClinicalTrials.gov, identifiers NCT00266487 and NCT00354081, respectively. The main objective in these trials was to study the effects of homocysteine-lowering therapy with folic acid and vitamin B12 to reduce the risk of cardiovascular events in patients with established coronary artery disease. The B-vitamin intervention, which included vitamin B6 in a 2x2 factorial design, was identical in the two trials. Follow-up was terminated for NORVIT on March 31st 2004 and for WENBIT October 5th 2005. Results from the NORVIT trial was published April 2006 {Bonaa, 2006} and preliminary results from the WENBIT trial were presented at the annual congress of the European Society of Cardiology September 4th 2007 {Zegers, 2007}. The WENBIT trial is completed and submitted for publication early in year 2008.

So far, none of the B-vitamin intervention trials have shown any statistically significant favourable effect of homocysteine-lowering therapy with folic acid with or without concomitant vitamin B12 on cardiovascular events {Bazzano, 2006}. In NORVIT there was even a trend towards an increased risk of cardiovascular events (myocardial infarctions) in patients receiving the combination of folic acid, vitamin B12 and vitamin B6. This trend was not observed in WENBIT. However, the treatment with folic acid / B12 was associated With a more rapid progression of angiographic coronary atenoses {Løland, 2010}. Thus, the "homocysteine-hypothesis" of vascular disease has been attenuated through the emergence of these negative trial results, whereas a potential harmful effect of the B-vitamin intervention has been revealed.

There is so far no data on possible long-term effects following years of B-vitamin supplementation. By combining analyses and follow-up in the NORVIT and WENBIT cohorts, we will probably have some more answers both considering possible subgroup and long-term effects of the B-vitamin intervention.

Current data indicate that folate prevents cancer, especially breast and colorectal cancer. However, during the last few years several reports have challenged this assumption. Swedish observational studies found increased risk of colorectal cancer at high blood folate levels {Van Guelpen, 2006} and increased risk of prostate cancer at high levels of folate and vitamin B12 {Hultdin, 2005}. In a randomised trial with folic acid versus placebo to prevent colorectal adenomas, one found increased risk of cancer in the group receiving folic acid, especially of prostate cancer {Cole, 2007}. In a long-term follow-up of women taking high doses of folic acid throughout pregnancy one found a doubled risk of deaths attributable to breast cancer {Charles, 2004}. Recently it has been hypothesized that the implementation of folic acid fortification of foods may have been wholly or partly responsible for the observed increase in colorectal cancer rates in the USA and Canada in the mid to late 1990s {Mason, 2007}. This has led to new hypotheses that folate may prevent carcinogenesis but may enhance the growth of established cancer cells {Ulrich, 2007}. The question of possible adverse effects of folic acid supplementation will be of major importance when public health administrations decide whether to implement or enhance programs folic acid fortification of foods.

The effect of the B-vitamin intervention will also be studied in relation to other life-style diseases like diabetes and osteoprosis.

Additionally, the combined NORVIT-WENBIT cohort will used for observational studies evaluating new risk phenotypes or genotypes and their potential effect modification by the B-vitamin interventions.

NORVIT and WENBIT - Long-term Follow-up

Combined Analyses and Long-term Follow-up in the Two Norwegian Homocysteine-Lowering B-Vitamin Trials NORVIT and WENBIT

University of Tromso

Norwegian Foundation for Health and Rehabilitation

Haukeland University Hospital

MD, PhD

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Gestational Trophoblastic Disease

Hydatidiform Mole

Nevus

Trophoblastic Neoplasms

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Pregnancy Complications

Pregnancy Complications, Neoplastic

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Antineoplastic Agents

Dermatologic Agents

Reproductive Control Agents

Chrysarobin

Methotrexate

Liver Extracts

Trace Elements

Antimetabolites

Enzyme Inhibitors

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Chemoprohylaxis Group: the treatment group, will be given a single course of methotrexate within fourteen days from molar evacuation. Methotrexate will be given at 0.4 mg/kg intramuscularly per day for 5 days. No chemotherapy will be administered if the hemoglobin is lower than 10 g/L, WBC is less than 3.0 x 10 g/L or more than 10.0 x 10 g/L, absolute neutrophil count is less than 1.5, platelet count is lower than 100,000/cu.cc., patient has elevated liver and renal function test and has concurrent infection.

Control Group: will be given a placebo in a form of Vitamin B Complex (Bee ALL), intramuscularly or intravenously.

Patients will be given a single course of methotrexate within fourteen days from molar evacuation.

Patients will be given a placebo in a form of Vitamin B Complex (Bee ALL), intramuscularly or intravenously.

Agnes L. Soriano-Estrella, MD

A randomized, controlled trial to evaluate the efficacy of methotrexate for the prevention of postmolar gestational trophoblastic disease among patients with high-risk hydatidiform mole.

A randomized, controlled trial to evaluate the efficacy of methotrexate for the prevention of postmolar gestational trophoblastic disease among patients with high-risk hydatidiform mole.

Women who will undergo suction curettage for complete hydatidiform mole at the Philippine General Hospital, who are at risk for developing postmolar gestational trophoblastic disease will be included in the study. Patients will receive either a single course of methotrexate or vitamin B complex (Benutrex) within fourteen days from molar evacuation. Patients' serum beta HCG will be monitored 1 week after molar evacuation and then every 2 weeks until the titers become normal for three consecutive determinations, then monthly for 6 months (every 2 months for the next 6 months).

RCT on the Efficacy of Methotrexate for the Prevention of GTD

The Efficacy of Methotrexate for the Prevention of Postmolar Gestational Trophoblastic Disease Among Patients With High-Risk Hydatidiform Mole

1. Diagnosis of postmolar gestational trophoblastic diseases will be based on the occurrence of any of the following conditions:

   * high level of hCG more than 4 weeks post-evacuation (serum level of 20,000mlU/m)
   * progressively increasing or plateuing hCG values at any time after evacuation (minimum of 3 weekly determinations)
   * clinical or histologic evidence of metastasis at any site
   * persistently elevated hCG titer at 14 weeks post-evacuation
   * elevation of previously normal hCG titer after evacuation provided the diagnosis of pregnancy is excluded
2. Toxicity brought about by the administration of methotrexate will be graded based on the WHO toxicity scoring system.

University of the Philippines

Blood and Lymph Conditions

Immune System Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hyperbilirubinemia

Lymphoma

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Other Dietary Supplements

Inotuzumab Ozogamicin

Pegaspargase

Asparaginase

Carnitine

Patients receive levocarnitine IV over 2-3 minutes every 6 hours up to 4 times a day (inpatient) or PO TID (outpatient). Patients also receive vitamin B complex PO BID. Treatment continues for up to 30 days after the last dose of either PEG-asparaginase or inotuzumab, or until Tbili of ≤ 1.5 x ULN or at least a 50% reduction in peak Tbili is achieved.

Levocarnitine

Elias Jabbour, MD

Elias Jabbour

This phase II trial studies how well levocarnitine and vitamin B complex works in treating abnormal high liver enzyme levels (hyperbilirubinemia) caused by treatment with PEG-asparaginase or inotuzumab ozogamicin in patients with acute lymphoblastic leukemia. Amino acids, such as levocarnitine, may work in normalizing liver enzyme levels due to treatment. Vitamin B complex is a dietary supplement that may be used for patients with nutritional deficiencies. Giving levocarnitine and vitamin B complex may work better in treating hyperbilirubinemia in patients with acute lymphoblastic leukemia.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of levocarnitine in combination with vitamin B complex in treating PEG-asparaginase (PEG) or inotuzumab ozogamicin (INO) induced hyperbilirubinemia (total bilirubin \[Tbili\] \> 3 x upper limit of normal \[ULN\]) in patients (pts) with acute lymphoblastic leukemia (ALL).

SECONDARY OBJECTIVES:

I. To evaluate chemotherapy dose intensity in patients treated with PEG-asparaginase or inotuzumab ozogamicin.

II. To characterize the safety, tolerability, and adverse event profile of levocarnitine and vitamin B for the treatment of hyperbilirubinemia.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

Patients receive levocarnitine intravenously (IV) over 2-3 minutes every 6 hours up to 4 times a day (inpatient) or orally (PO) three times a day (TID) (outpatient). Patients also receive vitamin B complex PO twice daily (BID). Treatment continues for up to 30 days after the last dose of either PEG-asparaginase or inotuzumab, or until Tbili of ≤ 1.5 x ULN or at least a 50% reduction in peak Tbili is achieved.

After completion of study treatment, patients are followed up at 30 days.

Levocarnitine and Vitamin B Complex in Treating PEG-Asparaginase or Inotuzumab Ozogamicin-Induced Hyperbilirubinemia in Patients With Acute Lymphoblastic Leukemia

Mitochondrial Cofactors for the Treatment of Hyperbilirubinemia Due to PEG-Asparaginase and or Inotuzumab Ozogamicin in Patients With Acute Lymphoblastic Leukemia (ALL)

The time to hyperbilirubinemia normalization or achieving at least a 50% reduction in peak total bilirubin will be compared to historical controls using the Log rank test. Competing risk analysis will be considered in the case that patients died before bilirubin normalization or at least a 50% reduction in peak total bilirubin is achieved.

Will be defined by normalization of hyperbilirubinemia. Response rates will be estimated along with the 95% confidence interval. The duration of time to hyperbilirubinemia normalization of at least 50% reduction in peak total bilirubin will be estimated using the Kaplan-Meier method.

Descriptive statistics will be used to summarize secondary endpoints. The incidence rates of binary secondary endpoints will be estimated, along with the 95% confidence intervals.

Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Descriptive statistics will be used to summarize secondary endpoints. The incidence rates of binary secondary endpoints will be estimated, along with the 95% confidence intervals. Safety data will be summarized by adverse event (AE) category, severity and frequency. The proportion of patients with AEs will be estimated.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
NORVIT and WENBIT - Long-term Follow-up	NCT00671346	Cancer Myocardial Infa... Cerebrovascular...		27 Years - 86 Years	Haukeland University Hospital
RCT on the Efficacy of Methotrexate for the Prevention of GTD	NCT01984099	Hydatidiform Mo...	Methotrexate Vitamin B Compl...	35 Years -	University of the Philippines
Levocarnitine and Vitamin B Complex in Treating PEG-Asparaginase or Inotuzumab Ozogamicin-Induced Hyperbilirubinemia in Patients With Acute Lymphoblastic Leukemia	NCT03564678	Acute Lymphobla... Hyperbilirubine...	Levocarnitine Vitamin B Compl...	18 Years -	M.D. Anderson Cancer Center
NORVIT and WENBIT - Long-term Follow-up	NCT00671346	Cancer Myocardial Infa... Cerebrovascular...		27 Years - 86 Years	Haukeland University Hospital
NORVIT and WENBIT - Long-term Follow-up	NCT00671346	Cancer Myocardial Infa... Cerebrovascular...		27 Years - 86 Years	Haukeland University Hospital
RCT on the Efficacy of Methotrexate for the Prevention of GTD	NCT01984099	Hydatidiform Mo...	Methotrexate Vitamin B Compl...	35 Years -	University of the Philippines

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