Clinical Studies

The Oral Therapy in Angina Pilot Study is designed to evaluate the effectiveness, alone or in combination, of oral liposomal phosphatidylcholine (Lipophos Forte), oral phosphatidylcholine admixed with EDTA (Lipophos EDTA), and oral DMSA (metal chelator), with or without the use of a negative field only magnetic sleep pad, on symptoms, carotid artery anatomy, stress echo, and laboratory findings in individuals with chronic stable angina who are receiving background antioxidant, mineral, and essential fatty acid nutritional support.  All subjects were under Dr. Roberts' care and had been treated previously with medical, nutritional, and in most cases interventional/surgical therapies.  All subjects were clinically stable at the time of enrollment.  Testing  and study treatments were provided at no cost.  Subjects were not compensated for their participation.  This is not a randomized, double blind, placebo or sham therapy controlled study.  This is a pilot study, designed to evaluate the efficacy of the above regimens in the setting of an Integrative Cardiology practice.  All of the therapies under study have been used by Dr. Roberts for at least five years (discussed in more detail elsewhere on this website and on our DVD presentations).  The stress echo and carotid IMT studies were carried out or read by Dr. Roberts, a board certified cardiologist, while the carotid ultrasounds were read by a board certified vascular surgeon.  The following diagnostic and evaluative studies (discussed elsewhere) were carried out at baseline and following six months of study treatment:

Symptom Severity as assessed by the Seattle Angina Questionnaire:
· Physical Limitation Scale       · Angina Stability Scale
· Angina Frequency Scale (looks at number of attacks per week and NTG requirement)
· Treatment Satisfaction Scale      · Quality of Life Scale      · Average Overall Score.
Higher scores reflect less severe symptoms; thus we wish to see a rise in score in response to study treatment

Functional Status as Assessed by Stress Echo:
· Treadmill time and time to angina
· Presence of ST depression and/or a deterioration in wall motion (from rest) as signs of effort induced myocardial ischemia

Carotid Ultrasound Findings:
· Mean and mean maximal intima media thickness (IMT) of the common carotid arteries (carried out in Dr. Roberts' office)
· Standard Carotid Ultrasound (separate study, carried out in the office of a vascular surgeon), to evaluate:
          ¨Flow velocity (the higher the velocity, the tighter the narrowing, the greater the impairment in blood flow - like your finger over the nozzle of a garden hose)
          ¨Plaque size (measured with digital calipers)
          ¨Percent stenosis, estimated form flow velocity and visual assessment of the images

Medication Requirements

Laboratory Assessment:
· Kidney (creatinine) and liver (AST) chemistries
· Lipids and Lipoprotein (a)
· High Sensitivity or Cardiac C-Reactive Protein (CRP), Fibrinogen (Fib), Homocysteine (Hcy), and HbA1c (index of blood sugar control over three months)

Heavy Metal Burden Estimate:
· Six hour urine metal spill following 500 mg of oral DMSA (a relatively weak chelator)

Treatment Protocols:
· All subjects received background nutritional support in the form of:
          ¨Broad spectrum, 6 tablet a day antioxidant and mineral (taken as two tablets three times a day)
          ¨Ethyl Ester EPA two daily (equivalent to four standard 1000 mg fish oil gelcaps)

· Group Three subjects were also treated with:
          ¨Lipophos Forte 900 mg every morning
          ¨Lipophos Forte 900 mg near bedtime 3 nights a week alternating with Lipophos EDTA 1/2 ounce (1/4 bottle) 4 nights per week 
          ¨20 Gauss negative field only magnetic sleep pad 

· Group Two subjects were also treated with:
          ¨Lipophos Forte 900 mg every evening near bedtime
          ¨DMSA 500 mg orally near bedtime 
          ¨20 Gauss negative field only magnetic sleep pad 

· Group One subjects were also treated with:
          ¨DMSA 500 mg at bedtime
          ¨Lipophos Forte 900 mg near bedtime  
          ¨No magnetic sleep pad 

All prior nutritional therapies were continued, but could be adjusted by Dr. Roberts as required based upon the patients' clinical condition.  Anti-angina and anti-hypertensive medications could be changed for any reason (tolerance or change in prescription coverage), but reductions in medication need typically reflects a clinical improvement.  Kidney and liver chemistries were repeated one month on treatment.  One subject could not tolerate oral DMSA and was switched to NDF (a nutritional metal binder that contains chlorella and cilantro).  One subject, with a 10 year history of  symptomatic coronary and asymptomatic carotid disease, to whom Dr. Roberts had offered catheterization/surgery on several occasions, initially improved on the study regimen.  Symptoms then increased and he was hospitalized under the care of another physician.  This individual left Dr. Roberts' practice and dropped out of the study (thus only 4 group three subjects).  No other events or regimen changes have occurred (as of 5/09).  The group findings will be determined and summarized after the study has been completed.  Three subject case reports are given below (without signifying which group the subject was in - this will be disclosed after the study has been completed)..

The case studies are interesting, and as the purpose of this study was to learn more about what works and what doesn't work, each subjects history and outcome will be presented, with emphasis placed on interesting findings.  Each case study will begin with a chart describing the subjects past cardiac history, followed by a narrative discussing the same.  Pre and post treatment findings will then be presented in chart form followed by a discussion of the same.
 

                                                                                                                     STUDY SUBJECTS

CJ Less angina and rapid resolution of a 38% carotid narrowing

BG Less angina with a 4:00 increase in treadmill time

FB Angina reduction with a 3:00 increase in treadmill time

Less angina and rapid resolution of a 38% carotid narrowing - CJ

CJ and I began working together in early 2007.  This 64 year old man sustained an inferior wall (right coronary artery) infarction 11 years earlier.  Six stents wee placed within the severely diseased RCA.  Three months later stents were placed in the Circumflex.  Additional stent procedures were required over the years, such that by early '07 CJ bore 15 stents within his coronary vasculature  We found CJ to have a markedly elevated lipoprotein (a), not a surprise given his history of premature coronary disease and restenosis, and a relatively low free testosterone level; treatment for both conditions was initiated.  Angiography revealed no lesions readily amenable to further stent intervention, and at this point CJ wasn't really excited about repetitive stent placement as the primary approach to his cardiovascular health care.  CJ' thus underwent a 35 hour program of EECP with excellent clinical results.  Amalgams fillings had been removed years earlier.   CJ had not previously undergone metal detoxification therapy and 21 IV EDTA treatments (strong lead and cadmium binder with limited avidity for mercury) were undertaken.  CJ also received 15 IV phosphatidylcholine (the same material administered in oral liposomal format within the study protocol).  He was on a comprehensive and well thought out nutritional program, which required only minimal modification on my part.  With all of these measures CJ had improved clinically, but angina had not fully resolved, and CJ continued to require an extensive medical regimen. 

Atrial flutter developed in late '08 during stress testing (his baseline stress test for this study).  His pre-study standard lipids looked good on the combination of niaspan 2000 mg, tricor 145 mg, and vytorin 10/40 (zetia 10 mg and simvastatin 40 mg). Diabetes was not a clinical issue, but CJ's HbA1c was mildly elevated at 6.1%.  Back pain was a clinical issue, and therapy with celebrex had been required for some time.  Celebrex can effect the kidney (as can many other meds, heavy metals, hypertension, and diabetes), and CJ's baseline creatinine was elevated at 1.51 (normal is £ 1.2).

CJ experienced no trouble with his treatment program.  Atrial flutter occurred on several occasions, but resolved with the addition of metoprolol to his program (as angina and hypertension improved, we were able to drop ranexa, nifedipine, and altace from CJ's program, "making room" for metoprolol).  Flushing related to high dose niaspan (2000 mg) became more of an issue; this agent was dropped and vytorin and tricor were continued for lipid control. 

 

PARAMETER				BASELINE				SIX MONTHS
Seattle Questionnaire Score				58				91
Treadmill Time				10:00				10:00
Time to Angina				No Angina				No Angina
St Depression				Yes				Yes
Deterioration in Wall Motion				Yes				No
LDL	HDL	Trigs	Lp(a)	80	39	153	46	90	33	326	50
A1c	CRP	Fib	Hcy	6.1	.33	282	11.9	5.7	.59	283	17.1
Creatinine		AST		1.51		35		1.43		28
CCA-mean		CCA-max		0.701		0.660		0.800		0.780
RICA Velocity		LICA Velocity		82/30		83/21		68/11		79/20
R % Stenosis		L % Stenosis		55%		38%		49%		0%
R Plaque		L Plaque		1.1 and 3.5		1.6 and 3.7		1.9 and 1.1		None

Subjectively and objectively, CJ improved.  His symptoms improved on a reduced medial regimen.  His lipids didn't improve (but do we care? is lipid reduction really the key? - await our immune mechanisms in atherosclerosis presentation), but CJ's IMT parameters improved accompanied by a gross reduction in carotid plaque burden.  This is a rapid and impressive response, in an individual who has been on intensive drug treatment for atherosclerosis for 11 years.  CJ and I both feel that this approach, the oral therapy for angina approach, worked a little better than would have a 16th stent.

Angina reduction with a 4:00 increase in treadmill time:  BG 

BG, a 63 year old man with medically controlled hypertension and type II diabetes, required stent placement in 2000 to deal with a high grade RCA narrowing.  Symptoms returned two years later.  A post-stent lesion had developed in the RCA; a second RCA stent was thus placed.  The circumflex had closed; this narrowing could not be addressed with a catheter based intervention.  Chest pain returned in 2004, increased in severity in 2005, but was stable when BG and I began working together in 2/07.  BG's amalgam fillings had been removed in 2002 but he had not received any medical metal binding therapy.  BG's LDL levels had been elevated (129 to 158), but BG did not wish to take statin therapy.  We looked a little deeper into BG's risk factor situation and found his Lp(a) to be above the 95th percentile at 59; this was addressed with lysine, proline, and vitamin C.  Testosterone deficiency, a typical finding in men with early onset coronary disease and diabetes was found, and pellet testosterone therapy initiated.  BG was already on a comprehensive and well thought out nutritional program; here I recommended an increase in arginine to 4000 mg three times a day and the addition of grape seed extract (facilitates conversion of arginine into nitric oxide) aiming to further improve endothelial function and nitric oxide generation.  I also offered to BG angiography, and if appropriate, bypass surgery or further stent placement, but he chose to continue with medical/nutritional therapy alone. 

With these measures BG improved, but his angina certainly did not resolve.  At the time of study entry, BG could walk for 5:00 on the treadmill.  Angina developed at 3:00.  ST depression was brought out.  BG's resting echo demonstrated findings of infarction over the inferior walls, consistent with a RCA heart attack.  Following treadmill stress wall motion deteriorated over the anterior segments, consistent with effort induced ischemia in the circumflex and LAD distributions.  His HbA1c had increased from 5.7 in '06 to 7.0, consistent with worsening blood sugar control.  His lipids remained elevated and his Lp(a) had increased (this parameter may vary greatly in some individuals and we cannot explain why - the key is to bind up this agent with lysine, proline, and vitamin C).  BG has no trouble following the study regimen (but he hasn't completed his paperwork nor has he returned his post-study DMSA metal result - so we will nag him until he does).

 

PARAMETER				BASELINE				SIX MONTHS
Seattle Questionnaire Score				52
Treadmill Time				5:00				9:00
Time to Angina				3:00				4:30
St Depression				Yes				Yes
Deterioration in Wall Motion				Yes				Yes
LDL	HDL	Trigs	Lp(a)	147	35	109	120	157	42	101	116
A1c	CRP	Fib	Hcy	7.0	1.1	334	8.1	5.6	1.2	332	13.6
CCA-mean		CCA-max		0.764		0.891		0.813		0.937
RICA Velocity		LICA Velocity		83/13		139/23		69/19		99/20
R % Stenosis		L % Stenosis		38%		35%		18%		30%
R Plaque		L Plaque		na		na		2.1 and 1.6		1.7 and 1.3

BG's functional status and angina severity improved considerably.  It takes far more effort to bring on angina (he participated in a game of vigorous volleyball without difficulty).  This symptomatic improvement is corroborated by an impressive increase in treadmill time, from 5:00 to 9:00, and an increase in exercise time to angina, from 3:00 to 4:30.  ST depression was still brought out and post-exercise wall motion was still abnormal.  Emotional stress may still bring on pain.  If BG decided to undergo angiography (and he doesn't) we would likely see multivessel disease, but blood flow has obviously improved, and done so in the relatively short time interval of six months.  Diabetes control improved, with an accompanying rise in HDL.  BG's carotid findings are conflicting.  Flow velocity fell, consistent with less resistance to flow and an increased flow area, but plaque size was unchanged to slightly increased (likely within measurement error), and estimated percent stenosis was also slightly increased.  BG's IMT findings also showed an increase.  BG was the first subject entered in the study, and our measuring techniques may not have been as accurate as later on when we had more experience with the pre and post-study testing.  Nonetheless BG's response to study therapy, added on to his prior medical and nutritional program, was quite positive.

Angina reduction with a 3:00 increase in treadmill time:  FB 

FB presented to us in 4/03 with three vessel occlusion, three closed or dysfunctional vein grafts, and evidence of a prior heart attack.  The only patent inflow route to his heart was a patent LIMA to LAD graft, allowing the LAD to give off collateral flow to the still viable heart muscle in the RCA and circumflex distributions.  Despite medical therapy with a beta blocker, a diuretic, and an ACEI, FB was experiencing angina on a daily basis.  This is a perfect scenario for EECP and FB did well with this treatment.  FB had a severe and essentially impossible to treat lipid abnormality; every statin had been tried and each one produced intolerable muscle pain.  We discovered an elevated Lp(a) and FB began Lp(a) binding therapy.  FB's testosterone was low.  FB felt better with supplementation but later stopped due to concern over potential side effects.  Nutritional therapy was applied as tolerated by FB.  FB does bear amalgam fillings.  He received brief courses of topical DMPS and oral Lipophos EDTA several years ago.  Just prior to study entry FB was experiencing angina once or twice a week.  Treadmill time was 5:08, with time to angina around 4:00 (I didn't write it down at the time and could be wrong here).  FB had no problems with the study protocol.

 

PARAMETER				BASELINE				SIX MONTHS
Seattle Questionnaire Score				68				96
Treadmill Time				5:08				8:08
Time to Angina				» 4:00				5:48
St Depression				Yes				Yes
Deterioration in Wall Motion				Yes				Yes
LDL	HDL	Trigs	Lp(a)	224	30	196	56	238	33	172	65
A1c	CRP	Fib	Hcy	6.8	3.4	362	12.1	6.9	4.9	382	11.4
Creatinine		AST		1.2		32		1.1		29
CCA-mean		CCA-max		0.649		0.742		0.667		0.797
RICA Velocity		LICA Velocity		49/14		93/24		62/10		69/15
R % Stenosis		L % Stenosis		50%		40%		50%		35%
R Plaque		L Plaque		2.2 and 3.1 mm		3.0 and 1.3 mm		3.1 and 1.6 mm		2.5 and 1.5 mm

Just as with BG, FB's treadmill time and time to angina increased, coupled with a reduction in angina frequency.  Las studies were without significant change.  Spills of lead, mercury, and aluminum decreased,.  Tin was brought out on the second study, reflecting interval clearing of mercury and other metals such that DMSA could now bring tin out.  FB's IMT values increased slightly, not consistent with the other findings, and again I wonder if our measurements were off.  The numbers don't show it, but modest carotid plaque reduction was felt to have occurred - quoting the report - "Comparing this study dated 1/02/09, with a previous study performed on 6/13/08, revealed the overall stenosis in the right carotid system to be unchanged with the one plaque remaining essentially the same; the other plaque apparently reduced itself in size from 2.3 mm to 1.6 mm.  In the left carotid system there is a reduction in the stenosis at the bulb bifurcation from 40% to 35% and a reduction of the anterior wall plaque from 3.0 mm to 2.5 mm".  This is all a positive outcome in a man with long standing, now inoperable angina and a chronically impossible to treat lipid abnormality.